JP2013540188A - Chain-extending polysiloxane crosslinker with dangling hydrophilic polymer chain - Google Patents

Abstract

The present invention relates to a straight chain comprising dangling hydrophilic polymer chains each covalently bonded to a divalent organic group separating each pair of two terminal ethylenically unsaturated groups, at least two polysiloxane segments and adjacent polysiloxane segments. A class of shape extending polysiloxane crosslinkers is provided. The present invention also relates to polymers comprising cross-linking units derived from the chain-extended polysiloxane cross-linking agent of the present invention and ophthalmic lenses comprising such polymers.

Description

  The present invention relates to a class of polymerizable chain-extended polysiloxanes having dangling hydrophilic polymer chains and uses thereof. The present invention also includes a polymer that is a polymer of a polymerizable chain-extended polysiloxane of the present invention and one or more other polymerizable compounds and a silicone made from a lens formulation that includes the polymerizable chain-extended polysiloxane of the present invention. The present invention relates to a hydrogel contact lens.

Background In recent years, soft silicone hydrogel contact lenses have become increasingly popular due to their high oxygen permeability and comfort. One of the lens forming materials widely used in producing silicone hydrogel contact lenses is polymerizable polysiloxane. The main function of the polymerizable polysiloxane is to provide high oxygen permeability to the resulting contact lens.

  However, it is known that polysiloxanes have a strong tendency to migrate to the surface of a substrate made of a material containing polysiloxanes to minimize the surface energy of the substrate. Contact lenses containing large amounts of polymerizable polysiloxanes generally exhibit insufficient wettability and generally require surface treatment.

  In addition, because of its hydrophobic nature, polymerizable polysiloxanes are generally used in hydrophilic compositions such as hydroxyethyl methacrylate, hydroxyethyl acrylate, N, N-dimethylacrylamide, N-vinyl pyrrolidone or internal wetting in lens formulations. Not compatible with the agent. It may be difficult to obtain a homogeneous lens formulation.

  Thus, it is relatively compatible with the hydrophilic components of lens formulations for making silicone hydrogel contact lenses and can improve the surface wettability of contact lenses made from such lens formulations. There is still a need for polymerizable polysiloxanes that can be made.

SUMMARY OF THE INVENTION The present invention, in one aspect, is a dangling wherein each is covalently bonded to a divalent organic group separating each pair of two terminal ethylenically unsaturated groups, at least two polysiloxane segments and adjacent polysiloxane segments. A linear chain extended polysiloxane crosslinker comprising a hydrophilic polymer chain is provided.

  In another embodiment, the present invention provides a polymer comprising polymer units derived from at least one polymerizable chain extended polysiloxane crosslinker of the present invention.

  In a further aspect, the present invention provides a silicone hydrogel contact lens comprising a polymeric material obtained by polymerizing a lens-forming material comprising the polymerizable chain-extended polysiloxane cross-linking agent of the present invention in a mold.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the terminology and experimental procedures used herein are well known in the art and commonly used. These procedures use conventional methods such as those provided in the art and various general references. Where a word is provided in the singular, the inventors also consider the plural of that word. The terminology used herein and the experimental procedures described below are well known and commonly used in the art.

  As used herein, “ophthalmic device” refers to contact lenses (hard or soft), intraocular lenses, corneal onlays, and other ophthalmic devices used on, around, or near the eye (eg, stents, Glaucoma shunt).

  “Contact lens” refers to a structure that can be placed on or within a wearer's eye. A contact lens can correct, improve, or change a user's vision, but this need not be the case. Contact lenses can be made of suitable materials known in the art or later developed and can be soft lenses, hard lenses or hybrid lenses. “Silicone hydrogel contact lens” refers to a contact lens comprising a silicone hydrogel material.

  “Hydrogel” or “hydrogel material” refers to a polymeric material that can absorb at least 10% by weight of water when fully hydrated.

  “Silicone hydrogel” refers to a silicone-containing hydrogel obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinyl monomer or crosslinking agent or at least one actinic radiation-crosslinkable silicone-containing prepolymer.

  As used herein, “hydrophilic” refers to a substance or portion thereof that more readily associates with water than with lipids.

  “Monomer” refers to a compound that can be polymerized chemically, actinically or thermally.

  As used herein, “vinyl monomer” refers to a monomer that has only one ethylenically unsaturated group and can be polymerized actinically or thermally.

  The terms “olefinically unsaturated group” or “ethylenically unsaturated group” are used herein in a broad sense and are intended to include groups containing at least one> C═C <group. Exemplary ethylenically unsaturated groups include, but are not limited to:

Contains allyl, vinyl, styryl or other C═C containing groups.

  “Actinic radiation” as used herein with respect to curing, crosslinking or polymerization of a polymerizable composition, prepolymer or material means that the curing (eg, crosslinking and / or polymerization) is actinic radiation, eg, UV radiation, It is carried out by ionizing radiation (for example, γ-ray or X-ray irradiation), microwave irradiation or the like. Methods of thermal curing or actinic curing are well known to those skilled in the art.

  The term “(meth) acrylamide” refers to methacrylamide and / or acrylamide.

  The term “(meth) acrylate” refers to methacrylate and / or acrylate.

  As used herein, “hydrophilic vinylic monomer” refers to a vinylic monomer that generally produces a polymer that is water soluble or can absorb at least 10% by weight of water as a homopolymer.

  As used herein, “hydrophobic vinyl monomer” refers to a vinyl monomer that, as a homopolymer, generally produces a polymer that is insoluble in water and can only absorb less than 10% by weight of water.

  “Prepolymer” refers to a polymer that contains ethylenically unsaturated groups and can be polymerized actinically or thermally to form a polymer having a higher molecular weight than the starting prepolymer.

  “Polymer” refers to a material formed by polymerizing / crosslinking one or more vinylic monomers, crosslinkers and / or prepolymers.

  As used herein, “molecular weight” of a polymeric material (including monomeric or macromeric materials) refers to the number average molecular weight unless otherwise indicated or unless the test conditions indicate otherwise.

  “Crosslinking agent” refers to a compound having at least two ethylenically unsaturated groups. “Crosslinking agent” refers to a compound belonging to the subclass of crosslinkers having at least two ethylenically unsaturated groups and having a molecular weight of 700 Daltons or less.

  The “polysiloxane vinyl monomer” refers to a vinyl monomer containing only one ethylenically unsaturated group and only one polysiloxane segment.

  “Chain extended polysiloxane vinyl monomer” refers to a compound comprising at least two polysiloxane segments separated by a single ethylenically unsaturated group and a bond.

  “Polysiloxane crosslinker” refers to a compound having at least two ethylenically unsaturated groups and a unique polysiloxane segment.

  “Chain extended polysiloxane crosslinker” refers to a linear polysiloxane compound comprising at least two ethylenically unsaturated groups and at least two polysiloxane segments separated by a bond.

  As used herein, the term “fluidity” refers to the ability of a substance to flow like a liquid.

  Free radical initiators can be either photoinitiators or thermal initiators. “Photoinitiator” refers to a chemical that initiates a free radical crosslinking / polymerization reaction by the use of light. Suitable photoinitiators include, but are not limited to, benzoin methyl ether, diethoxyacetophenone, benzoylphosphine oxides, 1-hydroxycyclohexyl phenyl ketone, Darocure® type photoinitiator and Irgacure® type. Photoinitiator, preferably Darocure® 1173 and Irgacure® 2959. Examples of benzoylphosphine oxide initiators are 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), bis- (2,6-dichlorobenzoyl) -4-N-propylphenylphosphine oxide and bis- (2,6 -Dichlorobenzoyl) -4-N-butylphenylphosphine oxide. Also suitable are reactive photoinitiators that can be incorporated into prepolymers or used as special monomers, for example. Examples of reactive photoinitiators are those disclosed in EP 632329, which is incorporated herein by reference in its entirety. Polymerization can then be induced by actinic radiation, for example light, in particular UV light of a suitable wavelength. If appropriate, the spectral requirements can be controlled accordingly by the addition of suitable photosensitizers.

  “Thermal initiator” refers to a chemical that initiates radical crosslinking / polymerization reaction through the use of thermal energy. Examples of suitable thermal initiators include, but are not limited to, 2,2′-azobis (2,4-dimethylpentanenitrile), 2,2′-azobis (2-methylpropanenitrile), 2,2′-azobis (2-methylbutanenitrile), peroxides such as benzoyl peroxide and the like. Preferably, the thermal initiator is 2,2'-azobis (isobutyronitrile) (AIBN).

  "Polymerizable UV absorber" refers to a compound comprising an ethylenically unsaturated group and a UV absorbing moiety capable of absorbing or shielding UV radiation in the range of 200 nm to 400 nm, as will be understood by those skilled in the art.

  The “bulky vinyl monomer” refers to a vinyl monomer having a bulky substituent. Preferred bulky vinyl monomers include, but are not limited to, N- [tris (trimethylsiloxy) silylpropyl] (meth) acrylamide; N- [tris (dimethylpropylsiloxy) silylpropyl] (meth) acrylamide; N- [tris (Dimethylphenylsiloxy) silylpropyl] (meth) acrylamide; N- [tris (dimethylethylsiloxy) silylpropyl] (meth) acrylamide; N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) Propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (Bis (tri Tylsilyloxy) methylsilyl) propyloxy) propyl] -2-methylacrylamide; N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] acrylamide; N- ( 2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) -2-methylacrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy ) Propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] -2-methylacrylamide; N, N-bis [2-hydroxy-3 -(3- (Tris (trimethylsilyloxy) ) Silyl) propyloxy) propyl] acrylamide; N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; N- [2-hydroxy-3- ( 3- (t-butyldimethylsilyl) propyloxy) propyl] acrylamide; N, N-bis [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] -2-methylacrylamide; N , N-bis [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] acrylamide; 3-methacryloxypropylpentamethyldisiloxane; tris (trimethylsilyloxy) silylpropyl methacrylate (TRIS); (3-methacryloxy-2-hydroxypro (Luoxy) propylbis (trimethylsiloxy) methylsilane); (3-methacryloxy-2-hydroxypropyloxy) propyltris (trimethylsiloxy) silane; 3-methacryloxy-2- (2-hydroxyethoxy) -propyloxy) propylbis (Trimethylsiloxy) methylsilane; N-2-methacryloxyethyl-O- (methyl-bis-trimethylsiloxy-3-propyl) silylcarbamate; 3- (trimethylsilyl) propyl vinyl carbonate; 3- (vinyloxycarbonylthio) propyl- Tris (trimethylsiloxy) silane; 3- [Tris (trimethylsiloxy) silyl] propyl vinylcarbamate; 3- [Tris (trimethylsiloxy) silyl] propylallylcarbamate; 3- [Tris (Trimethylsiloxy) silyl] propyl vinyl carbonate; t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinyl carbonate; trimethylsilylmethyl vinyl carbonate; t-butyl (meth) acrylate, cyclohexyl acrylate, isobornyl methacrylate, polysiloxane-containing vinyl System monomers (having 3 to 8 silicone atoms), and combinations thereof.

  As used herein with respect to polysiloxanes or compounds, the term “ethylenically functionalized” refers to the coupling of one or more ethylenic groups by using an ethylenically functionalized vinyl monomer. It is intended to refer to being covalently bonded to the polysiloxane or compound via the terminal (or pendant) reactive functional group of the polysiloxane or compound according to the reaction.

  An “ethylenically functionalized vinyl monomer” refers to a vinyl monomer having one reactive functional group that can participate in a coupling (or crosslinking) reaction known to those skilled in the art.

“Coupling reaction” refers to various reaction conditions well known to those skilled in the art, such as redox conditions, dehydration condensation conditions, addition conditions, substitution (or replacement) conditions, Diels-Alder reaction conditions, cationic crosslinking conditions, It is intended to refer to any reaction between a pair of matching reactive groups in the presence or absence of a coupling agent to form a covalent bond under ring conditions, epoxy cure conditions and combinations thereof. Preferably an amino group (as defined above -NHR '), hydroxyl group, carboxylic acid group, acid halide group (-COX, X = Cl, Br or I), acid anhydride group, aldehyde group, azlactone group, isocyanate group Non-limiting coupling reactions under various reaction conditions between a pair of matching co-reactive functional groups selected from the group consisting of: an epoxy group, an aziridine group, a thiol group and an amide group (—CONH ₂ ) Examples are given below for illustration. Carboxylic acid groups include coupling agents carbodiimides (eg 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), N, N′-dicyclohexylcarbodiimide (DCC), 1-cyclohexyl-3- (2-morpholino). In the presence of ethyl) carbodiimide, diisopropylcarbodiimide or mixtures thereof) to react with the amino group -NHR 'to form an amide bond; under heating, the carboxylic acid group reacts with an isocyanate group to form an amide bond; A carboxyl group reacts with an epoxy or aziridine group to form an ester bond; a carboxyl group reacts with a halide group (—Cl, —Br or —I) to form an ester bond; an amino group reacts with an aldehyde group To form a Schiff base that can be further reduced; 'Reacts with an acid chloride or acid bromide group or an acid anhydride group to form an amide bond (-CO-NR'-); an amino group -NHR' reacts with an isocyanate group to react with a urea bond (-NR'- C (O) —NH—); the amino group —NHR ′ reacts with an epoxy or aziridine group to form an amine bond (C—NR ′); the amino group reacts with an azlactone group (ring-opening reaction) To form a bond (—C (O) NH—CR ₁ R ₂ — (CH ₂ ) _r —C (O) —NR′—); the amino group is a halide group (—Cl, —Br or —I). ) To form an amine bond; hydroxyl reacts with an isocyanate to form a urethane bond, and hydroxyl reacts with an epoxy or aziridine or halide group (—Cl, —Br or —I) to form an ether bond (— O-); Le reacts with acid chloride or acid bromide group or acid anhydride group to form an ester bond; hydroxyl groups, the presence of a catalyst, bond by reacting with the azlactone group (-C (O) NH-CR 1 R _2- (CH ₂ ) _r —C (O) —O—); the thiol group (—SH) reacts with the isocyanate to form a thiocarbamate bond (—N—C (O) —S—). A thiol group reacts with an epoxy or aziridine to form a thioether bond (-S-); a thiol group reacts with an acid chloride or bromide group or an acid anhydride group to form a thioester bond; In the presence of an azlactone group to form a bond (—C (O) NH-alkylene-C (O) —S—); the thiol group is based on the thiol-ene reaction under thiol-ene reaction conditions. Vinyl group To form a thioether bond (-S-); a thiol group reacts with an acryloyl or methacryloyl group based on Michael addition under appropriate reaction conditions to form a thioether bond.

  It will also be appreciated that a coupling agent having two reactive functional groups may be used in the coupling reaction. The coupling agent having two reactive functional groups can be diisocyanate, diacid halide, dicarboxylic acid compound, diacid halide compound, diazlactone compound, diepoxy compound, diamine or diol. Those skilled in the art will recognize coupling reactions (eg, any of those previously described herein) to prepare polysiloxanes that are terminally modified with one or more ethylenically unsaturated groups, and the like. Knows well to choose the conditions. For example, diisocyanates, diacid halides, dicarboxylic acids, diazlactones or diepoxy compounds can be used to couple two hydroxy groups, two amino groups, two carboxyl groups, two epoxy groups, or combinations thereof; Diamine or dihydroxyl compounds can be used to couple two isocyanates, epoxies, aziridines, carboxylic acids, acid halide compounds or azlactone groups or combinations thereof.

Any suitable C ₄ -C ₂₄ diisocyanate can be used in the present invention. Examples of preferred diisocyanates include, but are not limited to, isophorone diisocyanate, hexamethyl-1,6-diisocyanate, 4,4′-dicyclohexylmethane diisocyanate, toluene diisocyanate, 4,4′-diphenyl diisocyanate, 4,4′-diphenylmethane diisocyanate. P-phenylene diisocyanate, 1,4-phenylene-4,4′-diphenyl diisocyanate, 1,3-bis- (4,4′-isocyanatomethyl) cyclohexane, cyclohexane diisocyanate and combinations thereof.

Suitable diamines can be used in the present invention. The organic diamines, linear or branched C ₂ -C ₂₄ aliphatic diamines, C ₅ -C ₂₄ cycloaliphatic or aliphatic cycloaliphatic diamines or C ₆ -C ₂₄ aromatic or alkyl aromatic diamines Can be similar. Preferred organic diamines are N, N′-bis (hydroxyethyl) ethylenediamine, N, N′-dimethylethylenediamine, ethylenediamine, N, N′-dimethyl-1,3-propanediamine, N, N′-diethyl-1 , 3-propanediamine, propane-1,3-diamine, butane-1,4-diamine, pentane-1,5-diamine, hexamethylenediamine and isophoronediamine.

  Any suitable diacid halide can be used in the present invention. Examples of preferred diacid halides include, but are not limited to, fumaryl chloride, suberoyl chloride, succinyl chloride, phthaloyl chloride, isophthaloyl chloride, terephthaloyl chloride, sebacoyl chloride, adipoyl chloride, trimethyladipoyl chloride, azela oil chloride, dodecanedioyl chloride , Succinyl chloride, glutaryl chloride, oxalyl chloride, dimer acid chloride and combinations thereof.

  Any suitable diepoxy compound can be used in the present invention. Examples of preferred diepoxy compounds are neopentyl glycol diglycidyl ether, 1,4-butanediol diglycidyl ether, 1,6-hexanediol diglycidyl ether, glycerol diglycidyl ether, ethylene glycol diglycidyl ether, diethylene glycol diglycidyl ether, Polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, dipropylene glycol diglycidyl ether and combinations thereof. Such diepoxy compounds are commercially available (eg, DENACOL series diepoxy compounds from Nagase ChemteX Corporation).

Suitable C ₂ -C ₂₄ diols (i.e., compounds having two hydroxyl groups) can be used in the present invention. Examples of preferred diols include, but are not limited to, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, propylene glycol, 1,4-butanediol, various pentanediols, various hexanediols, Includes various cyclohexanediols and combinations thereof.

Any suitable C ₃ -C ₂₄ dicarboxylic acid compound can be used in the present invention. Examples of preferred dicarboxylic acid compounds include, but are not limited to, linear or branched C ₃ -C ₂₄ aliphatic dicarboxylic acids, C ₅ -C ₂₄ alicyclic or aliphatic alicyclic dicarboxylic acids, C ₆ -C ₂₄ dicarboxylic acids containing aromatic or araliphatic dicarboxylic acids, amino or imide groups or N heterocyclic rings and combinations thereof. Examples of suitable aliphatic dicarboxylic acids are oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecadioic acid, dodecanedioic acid, dimethylmalonic acid, octadecyl succinate Acids, trimethyladipic acid and dimer acids (dimers of unsaturated aliphatic carboxylic acids such as oleic acid). Examples of suitable alicyclic dicarboxylic acids are 1,3-cyclobutanedicarboxylic acid, 1,3-cyclopentanedicarboxylic acid, 1,3- and 1,4-cyclohexanedicarboxylic acid, 1,3- and 1,4- Dicarboxylmethylcyclohexane, 4,4′-dicyclohexyldicarboxylic acid. Examples of suitable aromatic dicarboxylic acids are terephthalic acid, isophthalic acid, o-phthalic acid, 1,3-, 1,4-, 2,6- or 2,7-naphthalenedicarboxylic acid, 4,4′-diphenyl Dicarboxylic acid, 4,4′-diphenylsulfone dicarboxylic acid, 1,1,3-trimethyl-5-carboxyl-3- (p-carboxyphenyl) indane, 4,4′-diphenyl ether dicarboxylic acid, bis-p- (carboxyl) Phenyl) methane.

The appropriate C ₁₀ -C ₂₄ Jiazurakuton compounds can be used in the present invention. Examples of such diazlactone compounds are those described in US Pat. No. 4,485,236, which is hereby incorporated by reference in its entirety.

  The coupling reaction conditions are taught in textbooks and are well known to those skilled in the art.

  “Spatial limitation of actinic radiation” refers to US Pat. Nos. 6,800,225, 6,627,124, 7,384,590 and 7,387,759 (all by reference in their entirety). As shown in (incorporated herein), directing energy radiation in the form of light rays, for example by means of a mask or screen, or a combination thereof, to impinge on an area with a clear peripheral boundary in a limited space Or a process.

  "Dye" refers to a substance that is soluble in the lens-forming flowable material and used to impart color. The dye is generally translucent and absorbs light but does not scatter.

  “Pigment” refers to a powdered substance (particle) suspended in a lens-forming composition in which it is insoluble.

  “Hydrophilic surface” in the context of silicone hydrogel materials or contact lenses means that the silicone hydrogel material or contact lens is about 100 ° or less, preferably about 90 ° or less, more preferably about 80 ° or less, more preferably about It means having surface hydrophilicity characterized by an average water contact angle of 70 ° or less.

  “Average contact angle” refers to a water contact angle (measured by a droplet method) obtained by averaging measured values of at least three contact lenses.

  As used herein, an “antimicrobial agent” refers to a chemical that can reduce, eliminate, or inhibit microbial growth, as is known in the art. Preferred examples of antimicrobial agents include, but are not limited to, silver salts, silver complexes, silver nanoparticles, silver-containing zeolites and the like.

  “Silver nanoparticles” refers to particles made essentially of silver metal and having a particle size of less than 1 micrometer.

  The term “soluble” with respect to the polysiloxanes or prepolymers of the present invention refers to a solution of a prepolymer having a concentration of at least about 1% by weight at room temperature (about 22 ° C. to about 28 ° C.). It can be dissolved in a solvent to a sufficient extent to form.

According to the present specification, the term “oxygen permeability” for contact lenses is the estimated intrinsic oxygen corrected for the surface resistance to the oxygen flux produced by the boundary layer, measured according to the procedure described in Example 1. This refers to the transmittance Dk _c . The intrinsic “oxygen permeability” Dk of a material is the rate at which oxygen penetrates the material. Oxygen permeability is conventionally expressed in barrer units. "Barrer"
[(Cm ³ oxygen) (mm) / (cm ² ) (seconds) (mm Hg)] × 10 ⁻¹⁰
Is defined.

The “oxygen transmission rate” Dk / t of a lens or material is the rate at which oxygen passes through a specific lens or material of average thickness t (in mm) in the area being measured. Oxygen permeability is conventionally expressed in units of barrer / mm. "Barrer / mm"
[(Cm ³ oxygen) / (cm ² ) (seconds) (mm Hg)] × 10 ^-9
Is defined.

The “ion permeability” of a lens correlates with the ionoflux diffusion coefficient. The ionoflux diffusion coefficient D (in [mm ² / min] units) is determined by applying Fick's law as follows:
D = −n ′ / (A × dc / dx)
Where n ′ = ion transport rate [mol / min]; A = lens exposure area [mm ² ]; dc = concentration difference [mol / L]; dx = lens thickness [mm] is there.

  Generally, the present invention includes at least one 60% by weight of one or more hydrophilic monomers (preferably at least about 70% by weight, more preferably at least about 80% by weight, more preferably at least about 90% by weight). It relates to a class of actinically crosslinkable chain-extended polysiloxane crosslinkers having two or more polysiloxane segments, each pair covalently linked by a linker having hydrophilic polymer chains. The present invention is based, in part, on the discovery to prepare a crosslinkable linker having two reactive functional groups and at least one dangling hydrophilic polymer chain. Such crosslinkable linkers, on the other hand, can be used to prepare chain extended polysiloxane crosslinkers with well-defined structures.

  There are several potential unique features associated with the use of the chain extended polysiloxane crosslinkers of the present invention in the manufacture of silicone hydrogel contact lenses. First, the chain-extended polysiloxane crosslinker of the present invention in a silicone hydrogel contact lens formulation is a polymerizable polysiloxane with other hydrophilic components, such as hydrophilic vinylic monomers and optionally leachable polymer wetting agents. Can be used to significantly improve the suitability of It may be soluble in water, ophthalmically compatible solvents (eg 1,2-propylene glycol, polyethylene glycols having a molecular weight of about 400 Daltons or less or combinations thereof) or combinations thereof; It may be suitable for preparing silicone hydrogel lens formulations. Second, the chain-extending polysiloxane cross-linking agent of the present invention may be used to improve the surface wettability of silicone hydrogel lenses made from lens forming materials containing such chain-extending polysiloxane cross-linking agents. Good. Silicone hydrogel materials generally have a surface that is hydrophobic (non-wetting) or at least some areas of the surface. Hydrophobic surfaces or surface areas can absorb lipids and proteins from the ocular environment and adhere to the eye. Accordingly, silicone hydrogel contact lenses generally require surface modifications that are typically performed after lens casting. It is believed that the presence of dangling hydrophilic polymer chains along the polysiloxane (PDMS) chain can disperse the size of the hydrophobic regions on the lens surface and make the hydrophilic groups accessible for moisture. In addition, when the solution of the chain-extending polysiloxane crosslinking agent of the present invention is used as one of the polymerizable components in a lens formulation for producing a silicone hydrogel contact lens, It is believed that the ring hydrophilic polymer chain is preferably adsorbed at the interface between the mold for making contact lenses and the lens formulation. If dangling hydrophilic polymer chains are present in a sufficient amount in the cross-linking agent, an interfacial film consisting essentially of dangling hydrophilic polymer chains and having a sufficient thickness is formed before curing (polymerization). It is formed at the mold-formulation interface and can be preserved after curing. As such, a silicone hydrogel contact lens having a hydrophilic interface film thereon can be produced without surface treatment after curing. Third, the chain-extended polysiloxane cross-linking agent of the present invention may be used to improve the efficiency of lens extraction, particularly with water or an aqueous solution. In general, in order to remove unpolymerized components in the lens formulation, extraction of non-volatile residues from the lens produced by the monomer formulation is required. In the case of silicone hydrogel lenses, non-volatile extracts are usually extracted using organic solvents because of the solubility of silicone-containing extracts that are not sufficiently soluble in aqueous solutions. The presence of dangling hydrophilic polymer chains along the chain-extended polysiloxane chain can also increase the solubility of the extract in aqueous solution, in which case organic solvents in the extraction process can be minimized or eliminated. .

  The present invention, in one embodiment, is shared by (1) two terminal ethylenically unsaturated groups, (2) at least two polysiloxane segments, and (3) a divalent organic group that separates the at least two polysiloxane segments. A linear chain extended polysiloxane crosslinker is provided that includes at least one dangling hydrophilic polymer chain attached.

  In accordance with the present invention, the chain extended polysiloxane crosslinker is preferably of the formula (I)

[Where:
D ₀ , D ₁ , D ₂ and D ₃ are each independently of the formula (II)

{G ₅ is as defined below, and A ₁ , A ₂ , A ₃ and A ₄ are each independently a direct bond, linear or branched C ₁ -C ₁₀ alkylene divalent group. , — (CH (R ″) CH ₂ O) _r1 —CH (R ″) CH ₂ — (wherein R ″ is H or methyl, and r1 is an integer of 1 to 20) or C _{1 to} C ₇ alkyleneoxy C ₁ -C ₇ alkylene divalent group, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁ ′, R ₂ ′, R ₃ ′ , R ₄ ′, R ₅ ′, R ₆ ′, R ₇ ′ and R ₈ ′ are independently substituted with C ₁ -C ₈ alkyl, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy Phenyl, fluoro (C ₁ -C ₁₈ alkyl), -alk- (OCH ₂ CH ₂ ) _n -OR ₉ , wherein alk is a C ₁ -C ₆ alkylene divalent group, and R ₉ is C _1- C ₆ alkyl, n Is an integer from 1 to 20, a1 is an integer from 0 to 8, and m1, m2, p1, and p2 are each independently an integer from 0 to 150, and (m1 + p1) and (m2 + p2). Are independently 2 to 150}
A divalent group of
e1, e2, t1, t2 and t3 are each independently an integer of 0 or 1,
υ1, υ2 and υ3 are each independently an integer of 0 to 5, provided that (υ1 + υ2 + υ3) ≧ 1;
ω1, ω2 and ω3 are each independently an integer of 0 to 20, provided that (ω1 + ω2 + ω3) is an integer of 1 to 20,
L ₁ , L ₂ and L ₃ are each independently a direct bond,

R ₁₂ is hydrogen or C ₁ -C ₄ alkyl;
L ₁ ′, L ₂ ′ and L ₃ ′ are independent from each other,

R ₁₂ is as defined above, Y is —O— or —NR′—, where R ′ is hydrogen or C ₁ -C ₈ alkyl, and Y is T _1. , T ₂ or T ₃ ,
G _O , G ₁ , G ₁ ′, G ₁ ″, G ₂ , G ₂ ′, G ₂ ″, G ₃ , G ₃ ′, G ₃ ″, G ₄ and G ₅ are directly coupled to each other independently. or _{-Z 1 -X 1 -Z 2 -X 2} -Z 3 -X 3 -Z 4 - a divalent group, X _1, X ₂ and X ₃ independently of one another are a direct bond, -O -, -NR'-, -C (O) -NR'-, -NR'-C (O)-, -O-C (O) -NH-, -NH-C (O) -O-,- NR′—C (O) —NH—, —NH—C (O) —NR′—, —S—, —C (O) —O—, —O—C (O) —, —NH—C ( O) —NH—Z ₀ —NH—C (O) —NH—, —O—C (O) —NH—Z ₀ —NH—C (O) —O—, —O—C (O) —NH A bond selected from the group consisting of —Z ₀ —NH—C (O) —NH— and —NH—C (O) —NH—Z ₀ —NH—C (O) —O—, Z ₀ is a linear or branched C ₂ -C ₁₂ alkylene divalent group optionally containing one or more bonds of —O—, —NR′—, —S— and —C (O) —. Or a C ₅ -C ₄₅ alicyclic or aliphatic alicyclic divalent group, R ′ is H or C ₁ -C ₈ alkyl, and Z ₁ , Z ₂ , Z ₃ and Z ₄ are independently a direct bond, optionally -O -, - NR '-, - S- and -C (O) - of one or more linear contains therein a bond or branched C ₁ -C ₁₈ alkylene divalent radical, C ₁ -C ₇ alkyleneoxy C ₁ -C ₇ alkylene divalent radical, - (CH (R ") CH 2 O) r1 -CH (R") CH 2 - (R " and r1 is divalent groups are as defined above), an unsubstituted phenylene divalent radical, C ₁ -C ₄ alkyl or C ₁ -C phenylenediacetic substituted with ₄ alkoxy diradical or C ₇ -C ₁₂ Arakire Diradical, optionally -O -, - NR '-, - S- and -C (O) - C ₅ comprising in one or more of the bonds of -C ₄₅ cycloaliphatic or aliphatic alicyclic diacid divalent group, C ₆ -C was ₂₄ aromatic or araliphatic bivalent radical, or combinations thereof,
R ₁₀ and R ₁₁ are independently of each other hydrogen or C ₁ -C ₄ alkyl;

Is a linear or 3 containing at least about 60 wt% (preferably at least about 70 wt%, more preferably at least about 80 wt%, more preferably at least about 90 wt%) of one or more hydrophilic monomer units Arm-shaped (or Y-shaped) hydrophilic polymer chain,
T ₁ , T ₂ and T ₃ are each independently a linear or branched C _{2 to} C ₂₄ aliphatic trivalent group, C _{5 to} C ₃₀ alicyclic or aliphatic alicyclic ternary group. A C ₄ -C ₃₀ aliphatic heterocyclic trivalent group or a C ₃ -C ₂₄ aromatic or araliphatic trivalent group containing one or more oxygen or nitrogen atoms]
Defined by

In formula (II), R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ and R ₈ are preferably methyl.

  In a preferred embodiment, in formula (I), t1, t2 and t3 are integers of 1. Such a preferred chain-extended polysiloxane cross-linking agent comprises the following steps: (1) (a) mercaptan having only one thiol group and two first reactive functional groups (other than thiol groups), Michael addition or thiol Reacting with a monoethylenically functionalized hydrophilic polymer (ie a linear or three-armed hydrophilic polymer with only terminal ethylenically unsaturated groups) under ene reaction conditions, (b) monothiol termination Reacting a (linear or Y-shaped) hydrophilic polymer with a vinyl monomer having two first reactive functional groups (other than ethylenically unsaturated groups) under Michael addition or thiol-ene reaction conditions Or (c) a chain transfer agent (ie mercaptan) having only one thiol group and at least two first reactive functional groups, one or more hydrophilic vinyl At least about 60% by weight based monomer (preferably at least about 70% by weight, more preferably at least about 80% by weight, more preferably at least about 90% by weight) and one or more bulky vinylic monomers (any of the above) By polymerizing a mixture containing 0 to about 40 wt% (preferably 0 to about 30 wt%, more preferably 0 to about 20 wt%, more preferably 0 to about 10 wt%), a pendant (linear (Or three-armed) obtaining a crosslinked linker having a hydrophilic polymer chain and two first reactive functional groups; (2) coupling reaction conditions in the presence or absence of a coupling agent. At least one bifunctional polysiloxane having only one polysiloxane segment and two terminal second reactive functional groups At least one dangling hydrophilic polymer chain adapted to react to form an organic bond that couples two terminal first or second reactive functional groups, at least two polysiloxane segments and a pair of adjacent polysiloxane segments Forming an intermediate chain extended polysiloxane polymer having: and (3) a first capable of reacting with the first or second reactive functional group in the presence or absence of a coupling agent to form a covalent bond. By using an ethylenically functionalized vinyl monomer having three reactive functional groups (other than the ethylenically unsaturated group), the intermediate chain extended polysiloxane polymer is ethylenically functionalized, thereby producing the present invention. Can be obtained by a process comprising the step of forming a chain-extended polysiloxane crosslinker (of formula (I)) . Preferably, the first reactive functional group is selected from the group consisting of amino (—NHR ′, R ′ is as defined above), hydroxyl, carboxyl and combinations thereof; The reactive functional groups are independently of each other a hydroxyl group (—OH), an amino group (—NHR ′), a carboxyl group (—COOH), an isocyanate group, an epoxy group, an azlactone group, an aziridine group, an acid chloride and the like. Selected from the group consisting of

In another preferred embodiment, in formula (I), t1, t2 and t3 are 0. Such a preferred chain-extended polysiloxane cross-linking agent includes the following steps: (1) (a) C ₂ having three first reactive functional groups (which may be the same or different from each other) the C ₂₀ compound, in the presence or absence of a coupling agent, the coupling reaction conditions, with only one end of the second reactive functional group (linear or three arm-shaped) is reacted with a hydrophilic polymer Or (b) a C ₂ -C ₂₀ compound (reactive with an organic bromide) having three first reactive functional groups, an organic bromide as an ATRP initiator, at least about one or more hydrophilic vinylic monomers 60% by weight (preferably at least about 70% by weight, more preferably at least about 80% by weight, more preferably at least about 90% by weight) and one or more bulky vinylic monomers (above Any one) ATRP polymer obtained by polymerizing a mixture containing 0 to about 40 wt% (preferably 0 to about 30 wt%, more preferably 0 to about 20 wt%, still more preferably 0 to about 10 wt%) By reacting with a pendant (straight or three-armed) hydrophilic polymer chain and two first reactive functional groups selected from the group consisting of amino, hydroxyl, carboxyl, isocyanate groups and combinations thereof. Obtaining a crosslinkable linker having (2) a crosslinkable linker in the presence or absence of a coupling agent under a coupling reaction condition with a unique polysiloxane segment and two terminal third reactive functional groups. Reacting with at least one difunctional polysiloxane having two terminal first or third reactive functional groups, at least two Forming an intermediate chain-extended polysiloxane polymer having at least one dangling hydrophilic polymer chain bonded to an organic bond linking a pair of polysiloxane segments and adjacent polysiloxane segments; and (3) a coupling agent An ethylenic function having a fourth reactive functional group (other than an ethylenically unsaturated group) capable of reacting with the first or third reactive functional group to form a covalent bond in the presence or absence of The step of ethylenically functionalizing the intermediate chain-extended polysiloxane polymer by using a polymerizable vinyl-based monomer, thereby forming the chain-extended polysiloxane crosslinker of the present invention (ie, of formula (I)). It can be obtained by a method involving. Preferably, the second, third and fourth reactive functional groups are independently of each other a hydroxyl group (—OH), an amino group (—NHR ′), a carboxyl group (—COOH), an epoxy group, an isocyanate group. , An azlactone group, an aziridine group, an acid chloride, and combinations thereof.

  The term “ATRP” refers to atom transfer radical polymerization that includes an organic halide (eg, bromide) as an ATRP initiator that undergoes a reversible redox treatment catalyzed by a transition metal compound (eg, cuprous bromide).

  In a further preferred embodiment,

Are ethylene oxide units, (meth) acrylamide units, C ₁ -C ₃ alkyl (meth) acrylamide units, di (C ₁ -C ₃ alkyl) (meth) acrylamide units, N- vinyl pyrrole units, N- vinyl-2 pyrrolidone units, 2-vinyl oxazoline units, 4-vinylpyridine units, mono C ₁ -C ₄ alkoxy having a molecular weight of 600 daltons, mono (meth) acryloyl at the end stop polyethylene glycol units, di (C ₁ -C ₃ alkylamino) (C ₂ -C ₄ alkyl) (meth) acrylate units, N-C ₁ ~C ₄ alkyl-3-methylene-2-pyrrolidone units, N-C ₁ ~C ₄ alkyl-5-methylene -2 - pyrrolidone units, N- vinyl C ₁ -C ₆ alkyl amide units, N- vinyl -N-C ₁ ~C ₆ alkyl amide units and its At least about 60 wt% (preferably at least about 70 wt%, more preferably at least about 80 wt%, more preferably at least about 90 wt%) of one or more hydrophilic monomers selected from the group consisting of these combinations It is a linear or three-armed (or Y-shaped) hydrophilic polymer chain. Preferably, the linear or three-armed (or Y-shaped) hydrophilic polymer chain comprises a bulky vinyl monomer (any of the above). The linear or three-armed hydrophilic polymer chain has a molecular weight of about 10,000 daltons or less, preferably about 8,000 daltons or less, more preferably about 6,000 daltons or less, and even more preferably about 5,000 daltons or less. Have

Examples of preferred hydrophilic vinyl monomers used in embodiments of the present invention include N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), 3-acryloylamino-1-propanol, N- Methyl-3-methylene-2-pyrrolidone, N-ethyl-3-methylene-2-pyrrolidone, N-methyl-5-methylene-2-pyrrolidone, N-ethyl-5-methylene-2-pyrrolidone, 5-methyl- 3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1- Isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene- - pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, dimethylaminoethyl methacrylate (DMAEMA), N-vinyl-2-pyrrolidone (NVP), C ₁ ~C ₄ alkoxy having 1500 or less of the weight-average molecular weight Polyethylene glycol (meth) acrylate, methacrylic acid, N-vinylformamide, N-vinylacetamide, N-vinylisopropylamide, N-vinyl-N-methylacetamide, N-vinylcaprolactam and mixtures thereof.

  The above bulky vinyl monomers can be used in this embodiment of the invention.

  Mercaptan having 2 to 24 carbon atoms and two reactive functional groups selected from the group consisting of amino (—NHR ′, R ′ is as defined above), hydroxyl, carboxyl and combinations thereof Can be used in the present invention to prepare a crosslinker. Examples of such mercaptans include, but are not limited to, mercaptoglycerol, 2-mercapto-pyrimidine-4,6-diol; cysteine; 4-amino-5-mercaptopentanoic acid, 2-mercapto-4-amino-6 -Hydroxypyrimidine, 2-mercaptosuccinic acid, 3-mercapto-2- (methylamino) propanoic acid, 2-mercapto-4,5-dihydro-1h-imidazole-4,5-diol, 3-mercaptotyramine, mercaptopropane Diols, 2-mercaptomethylglutaric acid, 3-mercapto-DL-valine hydrochloride and combinations thereof.

  In the present invention, a vinyl monomer having two reactive functional groups selected from the group consisting of amino (—NHR ′, R ′ is as defined above), hydroxyl, carboxyl, and combinations thereof is used in the present invention. It can be used to prepare a crosslinked linker having pendant hydrophilic polymer chains. Examples of such vinyl monomers include, but are not limited to, N, N-2- (meth) acrylamide glycolic acid, glycerol (meth) acrylate, 2-hydroxy-3-aminopropyl (meth) acrylate, 1-hydroxy 2-aminopropyl (meth) acrylate, 1-amino-2-hydroxypropyl (meth) acrylate, glutaconic acid, itaconic acid, citraconic acid, mesaconic acid, maleic acid, fumaric acid and combinations thereof.

A linear hydrophilic polymer having only one thiol or ethylenically unsaturated group can be used in the present invention to prepare a crosslinked linker having a pendant hydrophilic polymer chain. Exemplary hydrophilic polymers having one ethylenically unsaturated group or thiol group include, but are not limited to, poly (ethylene glycol) (PEG) terminated with a monoethylenically unsaturated group or monothiol; Polyethylene glycol / polypropylene glycol (PEG / PPG) block copolymer terminated with an unsaturated group or monothiol; N, N-dialkyl (meth) acrylamide, N-vinylpyrrolidone, N-methyl-N-vinylacetamide, N - vinylacetamide, N- vinyl formamide, N- vinyl isopropylamide, di C ₁ -C ₄ alkylamino C ₂ -C ₄ alkyl (meth) acrylates, (meth) acrylamides, C ₁ ~ having a weight average molecular weight of 200 or less C ₄ alkoxy polyethylene glycol (meth) Selected from the group consisting of chlorate, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone or mixtures thereof and combinations thereof At least about 60 wt.% (Preferably at least about 70 wt.%, More preferably at least about 80 wt.%, More preferably at least about 90 wt.%); And one or more bulky Monoethylene containing 0 to about 40 wt% (preferably 0 to about 30 wt%, more preferably 0 to about 20 wt%, even more preferably 0 to about 10 wt%) of any vinyl monomer (any of the above) Polymer terminated with a polyunsaturated group or monothiol.

  Polyethylene glycols (PEG) terminated with monoethylenically unsaturated groups or monothiols are commercially available. The hydrophilic polymer terminated with monoethylenically unsaturated groups is the only reactive functional group selected from the group consisting of amino groups, hydroxyl groups, acid chloride groups, carboxyl groups, isocyanate groups, anhydrides and epoxy groups Can be prepared by ethylenically functionalizing a hydrophilic polymer having

  Various monofunctionally terminated PEGs can be obtained from commercial sources such as Shearwater Polymers, Inc. and Polymer Sources ™. A preferred monofunctional modified PEG is a PEG having one amino, hydroxyl, acid chloride or epoxy group at one end and a methoxy or ethoxy group at the other end. A variety of monofunctional polyvinylpyrrolidones (PVP) having a single terminal hydroxy, carboxyl or thiol group can be obtained from commercial sources such as Polymer Sources ™.

  Linear hydrophilic polymers terminated with one functional group of one or more hydrophilic vinylic monomers that do not contain a reactive functional group (other than an ethylenically unsaturated group) are hereby incorporated by reference in their entirety. Can be prepared according to procedures similar to those described in US Pat. No. 6,218,508, incorporated by reference. For example, one or more hydrophilic vinyl monomers that do not contain a functional group (ie, primary amino group, hydroxyl group, isocyanate group, carboxyl group, or epoxy group), a small amount (ie, based on the total amount of the polymerizable component) About 40% by weight or less, preferably about 30% by weight or less, more preferably about 20% by weight or less, more preferably about 10% by weight or less) of a bulky vinyl monomer and a chain transfer agent (eg 2-mercaptoethanol, 2 -Copolymerization (thermal or actinic) of aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid, thiolactic acid or other hydroxy mercaptans, amino mercaptans or carboxyl-containing mercaptans in the presence or absence of initiator )) Monohydroxy, monocarboxyl or monoa Get-terminated hydrophilic polymer or copolymer in emissions. In general, the molar ratio of chain transfer agent to one or more hydrophilic vinylic monomers is from about 1: 5 to about 1: 100. The molar ratio of chain transfer agent to hydrophilic vinylic monomer having no functional group is such that a polymer or copolymer having a molecular weight of about 500 to about 20,000, preferably about 750 to about 10,000 daltons is obtained. Selected. A polymer or copolymer terminated with one or more hydrophilic vinylic monomer monoepoxy, monoisocyanate or monoacid chloride was obtained according to known procedures with an epoxy, isocyanate or acid chloride group as described above, It can be prepared by covalent attachment to one or more hydrophilic vinylic monomer monohydroxy or monoamine terminated polymers or copolymers. The use of a hydrophilic polymer terminated with a monofunctional group having a higher molecular weight allows the silicone hydrogel material or the interfacial film on the lens made from the prepolymer of the present invention to have sufficient thickness and coverage. Can be guaranteed.

  Alternatively, the hydrophilic polymer terminated with a monofunctional group may contain one or more hydrophilic monomers (containing no reactive functional groups other than ethylenically unsaturated groups), hydroxyl, amine or carboxyl containing free radicals. It can be prepared by polymerization in the presence of initiator at an initiator: hydrophilic monomer molar ratio of about 1:30 to about 1: 700. Examples of initiators having an amine, hydroxyl or carboxy group are azo initiators such as 2,2′-azobis {2- [1- (2-hydroxyethyl) -2-imidazolin-2-yl] propane} dihydrochloride. Salt, 2,2′-azobis {2-methyl-N- [1,1-bis (hydroxymethyl) -2-hydroxyethyl] propionamide, 2,2′-azobis [2-methyl-N- (2- Hydroxyethyl) propionamide] or 2,2′-azobis {2-methyl-N- [2- (1-hydroxybutyl)] propionamide}, 2,2′-azobis (2-methylpropionamide) dihydrochloride 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] tetrahydrate.

  In accordance with the present invention, ethylenic functionalization of a hydrophilic polymer terminated with a monofunctional group can be accomplished by using an ethylenically functionalized vinyl-based monomer to convert an ethylenically unsaturated group with a monofunctional group. It can be carried out by covalently bonding to a functional group of the terminated hydrophilic polymer (eg amine, hydroxyl, carboxyl, isocyanate, anhydride and / or epoxy group). Any having hydroxy, amino, carboxyl, epoxy, aziridine, azlactone, acid chloride, isocyanate groups that are co-reactive with isocyanate, amine, hydroxyl, carboxy, anhydride or epoxy groups in the absence or presence of coupling agents Vinyl monomers can be used as ethylenically functionalized vinyl monomers.

Examples of ethylenically functionalized vinyl monomers include, but are not limited to, C ₂ -C ₆ hydroxylalkyl (meth) acrylate, C ₂ -C ₆ hydroxyalkyl (meth) acrylamide, allyl alcohol, allylamine, amino C _2- C ₆ alkyl (meth) acrylates, C ₁ -C ₆ alkylamino C ₂ -C ₆ alkyl (meth) acrylate, vinyl amine, amino C ₂ -C ₆ alkyl (meth) acrylamides, C ₁ -C ₆ alkylamino C ₂ ~ C ₆ alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₄ alkyl acrylic acid (eg methacrylic acid, ethyl acrylic acid, propyl acrylic acid, butyl acrylic acid), N- [tris (hydroxymethyl) methyl] acrylamide, N , N-2-acrylamidoglycolic acid, β-methylacrylic acid (chloro Acid), α-phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutacone Acid, aconitic acid, maleic acid, fumaric acid, aziridinyl C ₁ -C ₁₂ alkyl (meth) acrylate (eg 2- (1-aziridinyl) ethyl (meth) acrylate, 3- (1-aziridinyl) propyl (meth) acrylate), 4- (1-aziridinyl) butyl (meth) acrylate, 6- (1-aziridinyl) hexyl (meth) acrylate or 8- (1-aziridinyl) octyl (meth) acrylate), glycidyl (meth) acrylate, vinyl glycidyl ether, Allyl glycidyl ether, (meth) acrylic Halide group (-COX, X = Cl, Br or I), C ₁ -C ₆ isocyanatoalkyl (meth) acrylate, azlactone-containing vinyl monomer (e.g. 2-vinyl-4,4-dimethyl-1,3-oxazoline -5-one, 2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-ethyl-1,3-oxazolin-5-one, 2- Isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one, 2-vinyl-4,4-dibutyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl- 4-dodecyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-pentamethy 1,3-oxazolin-5-one, 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one, 2-vinyl-4,4-diethyl-1,3-oxazoline- 5-one, 2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-phenyl-1,3-oxazolin-5-one, 2 Isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, 2-vinyl-4,4-pentamethylene-1,3-oxazolin-5-one and 2-vinyl-4,4 -Dimethyl-1,3-oxazolin-6-one, preferably 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one (VDMO) and 2-isopropenyl-4,4-dimethyl-1 , 3-O Oxazoline-5-one (IPDMO)) and combinations thereof.

(It may be identical to each other, different also) three first reactive functional group Examples of C ₂ -C ₂₀ compounds with include, without limitation, 3-amino-1,2-propanediol Diol, 2-amino-1,3-propanediol, 2-amino-2-methylpropane-1,3-diol, α-aminoadipic acid, 2,3-dihydroxy-3-methylpentanoic acid, glyceric acid, 4 -Amino-2-hydroxybutanoic acid, 3-amino-2-hydroxypropionic acid, tyrosine, serine, threonine, lysine, aspartic acid, glutamic acid, 3-hydroxy-3-methylglutaric acid, malic acid, 2-hydroxyglutaric acid Glycerol, diglycerol, 1,1,1-trishydroxymethylethane, 1,1,1-trishydroxymethylpropane, 1, , 4-butanetriol, 1,2,6-hexanetriol, erythritol, pentaerythritol, diethylenetriamine, N-2′-aminoethyl-1,3-propylenediamine, N, N-bis (3-aminopropyl) amine, N, N-bis (6-aminohexyl) amine, triethylenetetramine, isocyanurate trimer of hexamethylene diisocyanate, 2,4,6-toluene isocyanate, p, p ′, p ″ -triphenylmethane triisocyanate , Isophorone diisocyanate trifunctional trimer (isocyanurate), trimesoyl chloride, cyclohexane-1,3,5-tricarbonyl chloride, trimer acid chloride, triglycidyl isocyanurate (TGIC), trimethylpropane trimethacrylate, pentae Tritoltetramethacrylate, triallyl isocyanurate, triallyl cyanurate, aconitic acid, citric acid, 1,3,5-cyclohexanetricarboxylic acid, 1,3,5-trimethyl-1,3,5-cyclohexanetricarboxylic acid, 1, 2,3-benzenetricarboxylic acid and 1,2,4-benzenetricarboxylic acid, preferably a bridge having a pendant (linear or three-armed) hydrophilic polymer chain and two first reactive functional groups C ₂ -C used to prepare the crosslinker (ie, in formula (I), t1 and t2 are zero and L ₁ , L ₂ , L ₁ ′ and L ₂ ′ are direct bonds) ₂₀ compounds are 3-amino-1,2-propanediol, 2-amino-1,3-propanediol, 2-amino-2-methylpropane-1,3-dio , Α-aminoadipic acid, 2,3-dihydroxy-3-methylpentanoic acid, lysine, aspartic acid or glutamic acid. Those skilled in the art are well aware of how to select a coupling reaction based on the selectivity and / or differential reactivity of a given functional group. For example, the amine group of 3-amino-1,2-propanediol is carbodiimide (ie, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), N, N′-dicyclohexylcarbodiimide (DCC)), In the presence of 1-cyclohexyl-3- (2-morpholinoethyl) carbodiimide, diisopropylcarbodiimide) according to the well-known carbodiimide-assisted coupling reaction and the only carboxyl group of the monofunctionalized linear or tri-armed hydrophilic polymer It can react to form a crosslinked linker with one dangling linear or three-armed hydrophilic polymer chain and two hydroxyl groups.

In accordance with the present invention, the three arms of the monofunctional tri-armed hydrophilic polymer, independently of one another, contain at least about 60% by weight of one or more hydrophilic monomers, preferably at least about 70% by weight, more preferably A linear hydrophilic polymer chain comprising at least about 80% by weight, more preferably at least about 90% by weight, and the hydrophilic monomers can be the same or different. Each arm, hydroxyl, amino, carboxyl, attached to the C ₂ -C ₂₀ compound having three first reactive functional group selected from the group consisting of isocyanate groups, and combinations thereof. A monofunctional three-arm hydrophilic polymer is a first linear hydrophilic polymer having a single terminal second reactive functional group and a C ₂ -C ₂₀ having three first reactive functional groups. React with the compound to form a linear hydrophilic polymer terminated with mono-di (first functional group), the second linear hydrophilic with only the third reactive functional group The polymer is reacted with a linear hydrophilic polymer terminated with mono-di (first functional group) to form a first and second bonded by a bond having one first reactive functional group. Forming an intermediate hydrophilic polymer composed of a linear hydrophilic polymer, and then converting the third linear hydrophilic polymer having a second reactive functional group at two ends into an intermediate hydrophilic polymer A three-armed hydrophilic poly having a unique terminal fourth reactive functional group It can be prepared by forming over. Preferably, C ₂ -C ₂₀ compound having three first reactive functional group for preparing monofunctional end-terminated 3-armed hydrophilic polymer, three different reactivity with different reactivity Contains functional groups such as 4-amino-2-hydroxybutanoic acid, 3-amino-2-hydroxypropionic acid, tyrosine, serine or threonine.

  Alternatively, a bridging linker having a pendant linear hydrophilic polymer chain and two first reactive functional groups (as described above) can be terminated with one monofunctional end under well-known coupling reaction conditions. It is also possible to sequentially react with the linear hydrophilic polymer and the linear hydrophilic polymer having two terminal functional groups to obtain a monofunctional end-terminated three-armed hydrophilic polymer.

  A three-armed hydrophilic polymer terminated with a monoethylenically unsaturated group can be transformed into a monofunctional group by using an ethylenically functionalized vinyl monomer (as described above). Can be prepared by covalently bonding to a functional group (eg, amine, hydroxyl, carboxyl, isocyanate, anhydride and / or epoxy group) terminated with a 3-armed hydrophilic polymer.

  Preparation of an intermediate chain-extended polysiloxane polymer having at least one dangling hydrophilic polymer chain bonded to an organic bond connecting two terminal reactive functional groups, at least two polysiloxane segments and a pair of adjacent polysiloxane segments In order to do this, suitable bifunctional polysiloxanes can be used. Various having two terminal functional groups selected from the group consisting of hydroxyl group (—OH), amino group (—NHR ′), carboxyl group (—COOH), epoxy group, isocyanate group, acid anhydride, and combinations thereof Polysiloxanes can be obtained from commercial sources (eg Gelest, Inc. or Fluorochem). Otherwise, one of ordinary skill in the art will follow the procedures known in the art and described in Journal of Polymer Science—Chemistry, 33, 1773 (1995), which is hereby incorporated by reference in its entirety. One will know how to prepare polysiloxanes terminated with such bifunctional groups. Examples of commercially available bifunctional polysiloxanes include, but are not limited to, polysiloxanes terminated with diepoxypropoxypropyl, polysiloxanes terminated with dihydroxyethoxypropyl, and terminated with dihydroxyl (polyethyleneoxy) propyl. Polysiloxane, dicarboxydecyl-terminated polysiloxane, dicarboxypropyl-terminated polysiloxane, dicaprolactam-terminated polysiloxane, di-N-ethylaminopropyl-terminated polysiloxane, Polysiloxanes terminated with diaminopropyl, polysiloxanes terminated with disuccinic anhydride, and combinations thereof. One skilled in the art will be familiar with selecting the bifunctional polysiloxane and coupling reaction conditions in step (2).

  In the coupling reaction mixture, the molar equivalent ratio of the crosslinked linker having one pendant hydrophilic polymer chain to the bifunctionally terminated polysiloxane is such that the resulting intermediate chain extended polysiloxane polymer is crosslinked. It will be appreciated that it can be determined whether one of the two reactive functional groups of the linker is capped or one of the two reactive functional groups of the bifunctional polysiloxane.

  If the molar equivalent ratio of the first crosslinker: first bifunctional terminated polysiloxane in the coupling reaction mixture is about 2: 1, the resulting first intermediate polysiloxane polymer is It has one polysiloxane segment and is capped with one of the two reactive functional groups of the crosslinker. The first intermediate polymer is then reacted with a second bifunctional polysiloxane (which can be different from or the same as the first bifunctional polysiloxane) at a molar equivalent ratio of 1: 2. Thus, a second intermediate polysiloxane polymer having three polysiloxane segments and capped with one of the reactive functional groups of the second bifunctional polysiloxane can be formed. Such a procedure can be repeated to obtain an intermediate polymer having the desired number of polysiloxane segments.

  Similarly, when the molar equivalent ratio of the first crosslinking linker: polysiloxane terminated with the first bifunctional group is about 1: 2 in the coupling reaction mixture, the resulting first intermediate polysiloxane The polymer has two polysiloxane segments and is capped with one of the two reactive functional groups of the first bifunctional polysiloxane. The resulting first intermediate chain-extended polysiloxane polymer can be ethylenically functionalized to obtain the chain-extended polysiloxane cross-linking agent of the present invention (ie, step (3)) or the second bridge. Reacted with a crosslinker (which can be different from or the same as the first crosslinker) at a molar equivalent ratio of 1: 2 to have the same two polysiloxane segments, but the second crosslinker A second intermediate polysiloxane polymer capped with one of the reactive functional groups can also be formed. Such a procedure can be repeated to obtain an intermediate polymer having the desired number of polysiloxane segments.

  New coupling linkers with two or more pendant hydrophilic polymer chains (ie, υ1 and ω1 are independent of each other) by covalently bonding two or three crosslinking linkers in the coupling reaction (any of the above) It will be understood that (which corresponds to formula (I) which is an integer of 2 or 3) can be formed.

Then, according to the ethylenic functionalization procedure, using the ethylenically functionalized vinyl monomer, the obtained intermediate chain-extended polysiloxane polymer is ethylenically functionalized, and the chain-extended polysiloxane crosslinking of the present invention is performed. An agent can be obtained. Preferably, the covalent bond formed in the ethylenic functionalization step is a bond that does not have an ester bond between one carbon-carbon double bond and one polydisiloxane segment. For example, when the terminal functional group of the intermediate chain-extended polysiloxane polymer is an amino or hydroxyl group, an azlactone-containing vinyl monomer or an isocyanate-containing (meth) acrylamide monomer (for example, C ₂ -C ₄ hydroxyalkyl (meth) acrylamide ( For example, hydroxyethyl (meth) acrylamide) and hexamethyl-1,6-diisocyanate (or can be a 1: 1 reaction product of isophorone diisocyanate or the above diisocyanate) are used as ethylenically functionalized vinyl monomers. If the terminal functional group of the intermediate chain extended polysiloxane polymer is an amino group, (meth) acrylic acid chloride can be used as the ethylenically functionalized vinyl monomer and the intermediate chain extended If terminal functional groups of the polysiloxane polymer is 1,2- or 1,3-diols, can be used acrylamide dimethyl acetal (or methacrylamide dimethyl acetal) as ethylenically functionalizing vinylic monomer.

  In this aspect of the invention, even though the various embodiments, including preferred embodiments of the invention, are described separately, they may be combined in any desired manner or used together to It will be appreciated that different embodiments of silicone hydrogel contact lenses can be envisaged.

  In another embodiment, the present invention relates to (1) a crosslinking unit derived from at least one chain-extended polysiloxane crosslinking agent having a dangling hydrophilic polymer chain; (2) hydrophilicity derived from at least one vinyl-based monomer. A chain transfer agent and / or vinyl having a unit and at least two ethylenically unsaturated groups; (3) a reactive functional group and an ethylenically unsaturated group each covalently bonded to the polymerizable unit via the reactive functional group (4) optionally, a hydrophobic unit derived from a hydrophobic vinyl monomer; and (5) a UV derived from a polymerizable UV absorber that is a further aspect of the present invention. A soluble amphiphilic prepolymer comprising an absorbing unit is provided. Such a prepolymer of the present invention comprises: (a) at least one chain-extended polysiloxane crosslinking agent; (b) at least one hydrophilic vinyl monomer; (c) a fourth reactive functional group (thiol). A vinyl monomer having a chain transfer agent and / or a fifth reactive functional group (other than an ethylenically unsaturated group) with or without (other than the group), (d) optionally a hydrophobic vinyl monomer, And (e) optionally polymerizing a polymerizable composition comprising a polymerizable UV absorber to form an intermediate copolymer and then reacting with the first or second reactive functional group to produce a coupling agent The intermediate copolymer is ethylenic with an ethylenically functionalized vinyl monomer having a sixth reactive functional group capable of forming a bond in a coupling reaction in the presence or absence. And the fourth, fifth and sixth reactive functional groups are independently of each other independently of the amino group -NHR ′ (where R ′ is as defined above). Selected from the group consisting of hydroxyl groups, carboxyl groups, acid halide groups, azlactone groups, isocyanate groups, epoxy groups, aziridine groups, and combinations thereof. US Pat. Nos. 6,039,913, 6,043,328, 7,091,283, 7,268, which have the same owner, are used to prepare such amphiphilic prepolymers. , 189, and 7,238,750, 7,521,519; U.S. Patent Application Publications US2008-0015315A1, US2008-0143958A1, US2008-0143003A1, US2008-0234457A1, US2008-0231798A1 having the same owner. As well as U.S. patent applications 12 / 313,546, 12 / 616,166 and 12 / 616,169, all of which are owned by the same; all of which are hereby incorporated by reference in their entirety. Incorporated.

  Various embodiments of chain-extending polysiloxane crosslinkers, ethylenically functionalized vinyl monomers, ethylenic functionalization reactions, coupling reactions and coupling agents have been described and are used in this aspect of the invention. be able to.

Any suitable hydrophilic vinylic monomer can be used in this embodiment of the invention. Suitable hydrophilic vinyl monomers include, but are not limited to, hydroxyl substituted C ₂ -C ₄ alkyl (meth) acrylates, hydroxyl substituted C ₁ -C ₄ alkyl vinyl ethers, C ₁ -C ₃ alkyl (meth) acrylamides, Di (C ₁ -C ₃ alkyl) (meth) acrylamide, N-vinylpyrrole, N-vinyl-2-pyrrolidone, 2-vinyloxazoline, 2-vinyl-4,4′-dialkyloxazolin-5-one, 2- And 4-vinylpyridine, olefinically unsaturated carboxylic acids having a total of 3 to 6 carbon atoms, amino-substituted C ₂ -C ₈ alkyl (the term “amino” also includes quaternary ammonium), mono (C ₁ -C ₃ alkylamino) (C ₂ -C ₄ alkyl) and di (C ₁ -C ₃ alkylamino) (C ₂ -C ₄ alkyl) (meth) acrylates, allyl Alcohol, N-C ₁ ~C ₄ alkyl-3-methylene-2-pyrrolidone, N-C ₁ ~C ₄ alkyl-5-methylene-2-pyrrolidone, N- vinyl C ₁ -C ₆ alkyl amide, N- vinyl —N—C ₁ -C ₆ alkylamides and combinations thereof.

Examples of preferred hydrophilic vinyl monomers are N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), 2-acrylamide glycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethyl. Acrylamide, N- [tris (hydroxymethyl) methyl] acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl-5-methylene-2-pyrrolidone, 1-isopropyl-3-methyl 2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl Methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium-2-hydroxypropyl methacrylate hydrochloride, aminopropyl methacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinyl pyridine, C ₁ -C ₄ alkoxy polyethylene les with 1,500 weight average molecular weight Glycol (meth) acrylate, N- vinyl formamide, N- vinyl acetamide, N- vinyl isopropylamide, N- vinyl -N- methylacetamide, N- vinyl caprolactam and mixtures thereof. Among these preferred hydrophilic vinyl monomers, those having no reactive functional group are particularly preferred for blending into a polymerizable composition for preparing an amphiphilic polysiloxane copolymer.

  Any suitable hydrophobic vinylic monomer can be used to prepare the soluble amphiphilic prepolymer of the present invention. Examples of preferred hydrophobic vinyl monomers include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, sec-butyl (meth) acrylate, isobutyl ( (Meth) acrylate, t-butyl (meth) acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, Butadiene, methacrylonitrile, vinyltoluene, vinylethyl ether, perfluorohexylethylthiocarbonylaminoethyl methacrylate, isobornyl methacrylate, trifluoroethylene Til methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate, silicone-containing vinyl monomers and mixtures thereof. Most preferably, the polymerizable composition comprises a bulky hydrophobic vinyl monomer that can be any of the above bulky hydrophobic vinyl monomers.

  The presence of such bulky hydrophobic vinylic monomers in the prepolymer used as one of the lens-forming materials is an optical defect (permanent deformation) resulting from handling during the manufacture of lenses made from lens-forming materials. ) Can be minimized or eliminated. Such deformations or optical defects can be attributed to the lens as described in Example 1 of co-pending US patent application Ser. No. 12 / 456,364 (incorporated herein by reference in its entirety). Permanent folds seen on the lens after being folded by hand and contact lens optical quality analyzer (CLOQA). When bulky hydrophobic vinylic monomers are present, the resulting lens exhibits a 'healing' effect that eliminates optical defects (ie, the folds are transient and in a short period of time, for example about 15 minutes or less. It can be disappeared).

  Any polysiloxane-containing vinyl monomer and crosslinking agent can be used in the present invention. The polysiloxane-containing vinyl monomer or cross-linking agent can be obtained from commercial sources or can be prepared according to known procedures. Examples of preferred polysiloxane-containing vinyl monomers and crosslinkers include, but are not limited to, polydimethylsiloxanes of various molecular weights terminated with mono (meth) acrylate (eg, terminated with mono-3-methacryloxypropyl). Monobutyl-terminated polydimethylsiloxane or mono (3-methacryloxy-2-hydroxypropyloxy) propyl-terminated and monobutyl-terminated polydimethylsiloxane); monovinyl-terminated and monovinyl carbonate Polydimethylsiloxanes of various molecular weights terminated or terminated with monovinylcarbamate; di (meth) acrylated polydimethylsiloxanes of various molecular weights (or so-called polysiloxane crosslinkers); terminated with divinyl carbonate Terminated polydimethylsiloxanes (polysiloxane crosslinkers); divinylcarbamate terminated polydimethylsiloxanes (polysiloxane crosslinkers); divinyl terminated polydimethylsiloxanes (polysiloxane crosslinkers); (Meth) acrylamide-terminated polydimethylsiloxanes (polysiloxane crosslinkers); bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane (polysiloxane crosslinkers); N, N, N ′, N '-Tetrakis (3-methacryloxy-2-hydroxypropyl) -α, ω-bis-3-aminopropyl polydimethylsiloxane (polysiloxane crosslinking agent); polysiloxanylalkyl (meth) acrylic monomer; glycidyl methacrylate and Amino functionality Reaction products with polydimethylsiloxanes; hydroxyl-containing polysiloxane vinyl monomers or crosslinkers; U.S. Pat. Nos. 4,136,250, 4,153,641, 4,182,822, 4, 189,546, 4,343,927, 4,254,248, 4,259,467, 4,260,725, 4,261,875, 4,355 147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, , 954,587, No.5,0 0,141, 5,034,461, 5,070,170, 5,079,319, 5,039,761, 5,346,946, 5,358, No. 995, No. 5,387,632, No. 5,416,132, No. 5,451,617, No. 5,486,579, No. 5,962,548, No. 5,981,675 6,039,913 and 6,762,264 (incorporated herein by reference in their entirety); crosslinkers containing polysiloxanes; disiloxanes comprising polydimethylsiloxanes and polyalkylene oxides And triblock macromers (eg, polyethylene oxide-block-polydimethylsiloxane-block-polyethylene oxide endcapped with methacrylate); And their mixtures.

  Preferred polymerizable UV absorbers include, but are not limited to, 2- (2-hydroxy-5-vinylphenyl) -2H-benzotriazole, 2- (2-hydroxy-5-acryloxyphenyl) -2H-benzotriazole, 2- (2-hydroxy-3-methacrylamideamido-5-tert-octylphenyl) benzotriazole, 2- (2′-hydroxy-5′-methacrylamidephenyl) -5-chlorobenzotriazole, 2- (2 ′ -Hydroxy-5'-methacrylamideamidophenyl) -5-methoxybenzotriazole, 2- (2'-hydroxy-5'-methacryloxypropyl-3'-t-butylphenyl) -5-chlorobenzotriazole, 2- ( 2'-hydroxy-5'-methacryloxyethylphenyl) benzotriazole, 2- (2 -Hydroxy-5'-methacryloxypropylphenyl) benzotriazole, 2-hydroxy-4-acryloxyalkoxybenzophenone, 2-hydroxy-4-methacryloxyalkoxybenzophenone, allyl-2-hydroxybenzophenone, 2-hydroxy-4-methacryl Contains oxybenzophenone. The polymerizable UV absorber is generally made from a lens-forming material comprising a prepolymer in a polymerizable composition for preparing a polysiloxane copolymer that is ethylenically functionalized on the other to obtain the polysiloxane prepolymer of the present invention. Sufficient to provide a contact lens that absorbs at least about 80% of UV light in the range of about 280 nm to about 370 nm impinging on the lens. One skilled in the art will understand that the specific amount of UV absorber used in the polymerizable composition depends on the molecular weight of the UV absorber and its extinction coefficient in the range of about 280 to about 370 nm. Let's go. In accordance with the present invention, the polymerizable composition comprises about 0.2% to about 5.0%, preferably about 0.3% to about 2.5%, more preferably about 0% by weight of UV absorber. From about 5% to about 1.8% by weight.

  Chain transfer agents (containing at least one thiol group) are used to control the molecular weight of the resulting intermediate copolymer. When the chain transfer agent does not contain a reactive functional group (other than thiol), a vinyl-based monomer having a reactive functional group (amine, hydroxyl, carboxyl, epoxy, isocyanate, azlactone or aziridine group) is a prepolymer of the present invention. Present in the polymerizable composition to prepare If the chain transfer agent has a reactive functional group, such as an amine, hydroxyl, carboxyl, epoxy, isocyanate, azlactone or aziridine group, it may be a terminal or pendant function for subsequent ethylenic functionalization of the resulting intermediate copolymer. Can be provided (amine, hydroxyl, carboxyl, epoxy, isocyanate, azlactone or aziridine groups). Vinyl-based monomers having reactive functional groups can provide another terminal or pendant hydroxyl, carboxyl or amino functionality to the resulting intermediate copolymer.

  In general, the molar ratio of chain transfer agent to one or more hydrophilic vinyl monomers is from about 1: 5 to about 1: 100, but the molar ratio of chain transfer agent to vinyl monomer having no reactive functional group is 1: 1. The molar ratio of chain transfer agent: vinylic monomer having no reactive functional group (eg, DMA, NVP) preferably has a molecular weight of about 500 to about 20,000, more preferably about 750 to about 10,000 daltons. The polymer or copolymer is selected to be obtained.

  The polymerizable composition for preparing the intermediate copolymer can be a melt, a solvent-free liquid blended with all necessary ingredients, or an inert solvent with all necessary ingredients as known to those skilled in the art (ie, Should not interfere with the reaction of the reactants in the mixture), for example, water, organic solvents or solutions dissolved in mixtures thereof.

  Examples of suitable solvents include, but are not limited to, water, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (eg acetone, methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethylene glycol. Methyl ether, ethylene glycol phenyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene glycol n-propyl ether, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-buty Ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dipropylene glycol dimethyl ether, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 1-propanol, 2-propanol, menthol, cyclohexanol, cyclopentanol, exo-norborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2- Butanol, 2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pe Butanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2 -Methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2--2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3 -Methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl -3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol, 4-propyl Pyr-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy- 3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol, 2,3,4-trimethyl- 3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol, 3-ethyl-3-pentanol, 1-ethoxy-2- Propanol, 1-methyl-2-propanol, tert-amyl alcohol, isopropanol, 1-methyl-2-pyrrolidone Including N, N- dimethylpropionamide, dimethyl formamide, dimethyl acetamide, dimethyl propionamide, and N- methylpyrrolidone and mixtures thereof.

  The copolymerization of the polymerizable composition to prepare the intermediate copolymer can be induced photochemically or preferably thermally. Suitable thermal polymerization initiators are known to those skilled in the art and include, for example, peroxides, hydroperoxides, azobis (alkyl or cycloalkyl nitriles), persulfates, percarbonates or mixtures thereof. Examples are benzoyl peroxide, tert-butyl peroxide, ditert-butyldiperoxyphthalate, tert-butyl hydroperoxide, azobis (isobutyronitrile) (AIBN), 1,1-azodiisobutylamidine, 1,1′- Azobis (1-cyclohexanecarbonitrile), 2,2'-azobis (2,4-dimethylvaleronitrile) and the like. The polymerization is conveniently carried out in the above-mentioned solvents at an elevated temperature, for example at a temperature of 25-100 ° C, preferably 40-80 ° C. The reaction time can vary within wide limits, but is conveniently for example 1 to 24 hours or preferably 2 to 12 hours. It is advantageous to degas the components and solvents used for the polymerization reaction in advance and to carry out the polymerization reaction under an inert atmosphere, for example under a nitrogen or argon atmosphere. Copolymerization can yield an optically clear, well-defined copolymer, which can be worked up in a conventional manner using techniques such as extraction, precipitation, ultrafiltration, etc. .

  Preferably, the intermediate copolymer has from about 15 wt% to about 70 wt%, preferably about 25 wt% of cross-linked units derived from at least one chain extended polysiloxane crosslinker having dangling hydrophilic polymer chains of the present invention. About 10% to about 60% by weight of hydrophilic units derived from one or more hydrophilic monomers, preferably about 15% to 45% by weight, one or more bulky hydrophobic vinyls 0 to about 30% by weight, preferably about 5% to about 25% by weight of a bulky hydrophobic unit derived from a monomer and 0 to about 5% by weight of a polymerizable UV absorber, about 0.2% by weight About 4% by weight, preferably about 0.5% to about 2.5% by weight. All the above% values are weight percent based on the total weight of all polymerizable components, including those not previously listed.

  The chain-extended polysiloxane crosslinkers of the present invention and the soluble amphiphilic prepolymers of the present invention can find particular use in preparing silicone hydrogel ophthalmic lenses, particularly contact lenses.

  In this aspect of the invention, even though the various embodiments, including preferred embodiments of the invention, are described separately, they may be combined in any desired manner or used together to It will be appreciated that different embodiments of silicone hydrogel contact lenses can be envisaged. All of the various embodiments described above with respect to previous aspects of the invention can be used in this aspect of the invention alone or in combination in any desired manner.

  In a further aspect, the present invention provides a soft contact lens. The soft contact lens of the present invention comprises a silicone hydrogel material obtained by curing the lens forming material in a mold, the lens forming material being a chain-extending polysiloxane crosslinker or a soluble amphiphilic prepolymer of the present invention. (As detailed above) as well as hydrophilic vinyl monomers, hydrophobic vinyl monomers, crosslinkers having a molecular weight of less than 700 Daltons, polymerizable UV absorbers, visual colorants (eg dyes, pigments or their A mixture), an antimicrobial agent (eg, preferably silver nanoparticles), a bioactive agent, a leachable lubricant, a leachable tear stabilizer, and mixtures thereof.

  In accordance with the present invention, the lens-forming material is a flowable composition that can be a solution or a melt at a temperature of about 20 ° C to about 85 ° C. Preferably, the lens-forming material is a solution of at least one prepolymer of the present invention and other desired components in water or an organic solvent or a mixture of water and one or more organic solvents.

  Various embodiments of chain-extending polysiloxane crosslinkers, soluble amphiphilic prepolymers, hydrophilic vinyl monomers, hydrophobic vinyl monomers, solvents, crosslinkers, polymerizable UV absorbers, photoinitiators are described They can be used in this aspect of the invention.

  Examples of crosslinkers include, but are not limited to, tetraethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, bisphenol A dimethacrylate, vinyl Methacrylate, ethylenediamine di (meth) acrylamide, glycerol dimethacrylate, allyl (meth) acrylate, N, N′-methylenebis (meth) acrylamide, N, N′-ethylenebis (meth) acrylamide, N, N′-dihydroxyethylenebis (Meth) acrylamide, 1,3-bis (methacrylamidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (N- (meth) acrylamidepropyl) 1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacrylamidobutyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacrylic) Oxyethylureidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, diamine (preferably N, N′-bis (hydroxyethyl) ethylenediamine, N, N′-dimethylenediamine, ethylenediamine, N, N′-dimethyl-1,3-propanediamine, N, N′-diethyl-1,3-propanediamine, propane-1,3-diamine, butane-1,4-diamine, pentane-1,5- Selected from the group consisting of diamine, hexamethylenediamine, isophoronediamine and combinations thereof. ) And the epoxy-containing vinyl monomer (preferably, glycidyl (meth) acrylate, vinyl glycidyl ether, is selected from the group consisting of allyl glycidyl ether and combinations thereof) with the product of any combination thereof. More preferred crosslinkers used in the preparation of the prepolymers of the present invention are tetra (ethylene glycol) diacrylate, tri (ethylene glycol) diacrylate, ethylene glycol diacrylate, di (ethylene glycol) diacrylate, glycerol dimethacrylate Allyl (meth) acrylate, N, N′-methylenebis (meth) acrylamide, N, N′-ethylenebis (meth) acrylamide, N, N′-dihydroxyethylenebis (meth) acrylamide or a combination thereof.

  The bioactive agent incorporated in the polymer matrix is any compound that can prevent eye disease or reduce symptoms of eye disease. The bioactive agent can be a drug, amino acid (eg, taurine, glycine, etc.), polypeptide, protein, nucleic acid, or any combination thereof. Examples of drugs useful herein include, but are not limited to, rebamipide, ketotifen, olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine, rhodoxamide, ketotifen, or pharmaceutically acceptable salts or esters thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha-hydroxylic acid (such as glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid and citric acid and their salts), linole Acid and γ-linoleic acid and vitamins (eg B5, A, B6, etc.).

  Examples of leachable lubricants include, but are not limited to, mucin-like materials (eg, polyglycolic acid) and non-crosslinkable hydrophobic polymers (ie, having no ethylenically unsaturated groups).

  Any hydrophilic polymer or copolymer having no ethylenically unsaturated groups can be used as the leachable lubricant. Preferred examples of non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohols (PVA), polyamides, polyimides, polylactones, homopolymers of vinyl lactams, the presence of one or more hydrophilic vinylic comonomers or Copolymer of at least one vinyl lactam in the absence, homopolymer of acrylamide or methacrylamide, copolymer of acrylamide or methacrylamide and one or more hydrophilic vinyl monomers, polyethylene oxide (ie polyethylene glycol (PEG)), poly Oxyethylene derivatives, poly-N, N-dimethylacrylamide, polyacrylic acid, poly-2-ethyloxazoline, heparin polysaccharides, polysaccharides and mixtures thereof.

The weight average molecular weight M _w of the non-crosslinkable hydrophilic polymer is preferably 5,000 to 500,000 daltons, more preferably 10,000 to 300,000 daltons, and even more preferably 20,000 to 100,000 daltons. .

  Examples of leachable tear stabilizers include, but are not limited to, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, glycosphingolipids, fatty alcohols, fatty acids, mineral oils and their Contains a mixture. Preferably, the tear stabilizer is a phospholipid, monoglycerides, diglycerides, triglycerides, glycolipid, glyceroglycolipid, sphingolipid, glycosphingolipid, fatty acid having 8 to 36 carbon atoms, 8 to 36 It is a fatty alcohol having carbon atoms or a mixture thereof.

  Lens molds for manufacturing contact lenses are well known to those skilled in the art and are used, for example, in casting or spin casting. For example, a mold (for casting) generally includes at least two mold sections (or portions) or mold halves, i.e., first and second mold halves. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive each other such that a lens molding cavity is formed between the first molding surface and the second molding surface. The molding surface of the mold half is the cavity forming surface of the mold and is in direct contact with the lens forming material.

  Methods for making mold sections for casting contact lenses are generally well known to those skilled in the art. The method of the present invention is not limited to a specific mold forming method. In fact, any mold forming method can be used in the present invention. The first and second mold halves can be formed by various techniques such as injection molding or turning. Examples of suitable methods for forming the mold halves are U.S. Pat. No. 4,444,711 to Schad, U.S. Pat. No. 4,460,534 to Boehm et al., Also incorporated herein by reference. No. 5,843,346 to Morrill and US Pat. No. 5,894,002 to Boneberger et al.

  Virtually all materials known in the art for making molds can be used to make molds for making contact lenses. For example, clear amorphous ethylene and norbornene from polymeric materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade 8007-S10 (eg Ticona GmbH (Frankfurt, Germany and Summit, New Jersey)) Quality copolymer) and the like. Other materials that allow UV light transmission, such as quartz glass and sapphire, can also be used.

In a preferred embodiment, a reusable mold is used and the lens-forming composition is actinically cured (ie, polymerized) to form a silicone hydrogel contact lens under the spatial limitation of actinic radiation. . Examples of preferred reusable molds are US patent application Ser. No. 08 / 274,942, filed Jul. 14, 1994, filed Dec. 10, 2003, which is incorporated herein by reference in its entirety. No. 10 / 732,566, US patent application Ser. No. 10 / 721,913 filed Nov. 25, 2003 and US Pat. No. 6,627,124. Reusable molds are quartz, glass, sapphire, CaF ₂ , cyclic olefin copolymers, such as Topas® COC grade 8007-S10 (Ticona GmbH (Frankfurt, Germany and Summit, New Jersey), ethylene and norbornene Clear amorphous copolymer), Zeon Chemicals LP (Louisville, KY) Zeonex® and Zeonor®, polymethyl methacrylate (PMMA), DuPon polyoxymethylene (Delrin), GE Plastics Ultem (registered trademark) (polyetherimide), PrimoSpire (registered trademark), and the like.

  According to the invention, the lens-forming material can be introduced (dispensed) into the cavity formed by the mold according to known methods.

  After the lens-forming composition is dispensed into the mold, it is polymerized to produce a contact lens. Crosslinking is initiated either thermally or actinically, preferably by exposing the lens-forming composition in the mold to the spatial limitations of the actinic radiation to crosslink the polymerizable component in the lens-forming composition. Can do.

  When the lens-forming composition includes a polymerizable UV absorber (ie, a UV-absorbing moiety-containing vinyl monomer), a benzoylphosphine oxide photoinitiator is preferably used in the present invention as a photoinitiator. Preferred benzoylphosphine oxide photoinitiators include, but are not limited to, 2,4,6-trimethylbenzoyldiphenylphosphine oxide; bis- (2,6-dichlorobenzoyl) -4-N-propylphenylphosphine oxide; and bis- ( 2,6-dichlorobenzoyl) -4-N-butylphenylphosphine oxide. It will be appreciated that any photoinitiator other than a benzoylphosphine oxide initiator may be used in the present invention.

  The opening of the mold for removing the molded product from the mold can be carried out in a manner known per se.

  The molded contact lens can be subjected to lens extraction to remove unpolymerized polymerizable components. The extraction solvent can be any solvent known to those skilled in the art. Examples of suitable extraction solvents are those described above. Following extraction, the lens can be hydrated in water or an aqueous solution of a wetting agent (eg, a hydrophilic polymer).

  The molded contact lens can be further processed, for example, surface treatment (eg, plasma treatment, chemical treatment, grafting of hydrophilic monomers or macromers on the lens surface, layer-by-layer coating, etc.), about 0.005% by weight Up to about 5% by weight of a wetting agent (eg, the hydrophilic polymer) and / or a viscosity enhancer (eg, methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose ( HPMC) or a mixture thereof) can be subjected to packaging, sterilization, etc. in a lens package containing a packaging solution.

  The contact lenses of the present invention preferably have an oxygen permeability of at least about 40 barrer, more preferably at least about 55 barrer, and even more preferably at least about 70 barrer. In accordance with the present invention, oxygen permeability is the apparent oxygen permeability measured according to the procedure described in the examples (eg, measured directly when testing a sample about 100 microns thick).

  The contact lens of the present invention is about 0.1 MPa to about 2.0 MPa, preferably about 0.2 MPa to about 1.5 MPa, more preferably about 0.3 MPa to about 1.2 MPa, and even more preferably about 0.4 MPa to It has an elastic modulus of about 1.0 MPa.

The contact lenses of the present invention are further preferably at least about 1.0 × 10 ⁻⁵ mm ² / min, more preferably at least about 2.0 × 10 ⁻⁵ mm ² / min, and even more preferably at least about 6.0 ×. It has an ionoflux diffusion coefficient D of 10 ⁻⁵ mm ² / min.

  The contact lenses of the present invention further preferably have a moisture content of from about 15 wt% to about 55 wt%, more preferably from about 20 wt% to about 38 wt% when fully hydrated. The water content of silicone hydrogel contact lenses can be measured according to the bulk technique disclosed in US Pat. No. 5,849,811.

  In this aspect of the invention, even though the various embodiments, including preferred embodiments of the invention, are described separately, they may be combined in any desired manner or used together to It will be appreciated that different embodiments of silicone hydrogel contact lenses can be envisaged. All of the various embodiments described above with respect to previous aspects of the invention can be used in this aspect of the invention alone or in combination in any desired manner.

  The above disclosure enables one skilled in the art to practice the invention. In order for the reader to better understand the specific embodiments and their advantages, reference to the following non-limiting examples is recommended. However, the following examples should not be read as limiting the scope of the present invention.

  Although various embodiments of the invention have been described using specific terms, apparatus, and methods, such description is for illustrative purposes only. The words used are for explanation purposes and not for limitation. It will be understood that changes and modifications may be made by those skilled in the art without departing from the spirit or scope of the invention as set forth in the claims. In addition, it will be understood that the various embodiments may be interchanged in whole or in part and may be combined in any manner or used together. Therefore, the spirit and scope of the following claims should not be limited to the description of the preferred embodiments contained herein.

Example 1
Oxygen permeability measurement US Pat. No. 5,760,100, which is incorporated herein by reference in its entirety, and references by Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, HD Cavanagh Ed., Raven Press: New York 1988, pp 273-280), the apparent oxygen transmission rate of the lens and the oxygen transmission rate of the lens material were measured. Oxygen flux using a Dk1000 instrument (commercially available from Applied Design and Development Co. (Norcross, GA)) or similar analytical instrument at 34 ° C. in a wet cell (ie, maintaining the airflow at about 100% relative humidity) (J) was measured. An air stream having a known oxygen percentage (eg 21%) is passed from one side of the lens at a rate of about 10-20 cm ³ / min and a nitrogen stream is passed from the opposite side of the lens at a rate of about 10-20 cm ³ / min. did. Samples were allowed to equilibrate at the specified test temperature in the test medium (ie, saline or distilled water) for at least 30 minutes and no more than 45 minutes prior to measurement. The test medium used as an overlayer was equilibrated at the specified test temperature for at least 30 minutes and not more than 45 minutes prior to measurement. The speed of the stirring motor was set to 1,200 ± 50 rpm corresponding to the instruction setting of 400 ± 15 on the step motor controller. The atmospheric pressure P _measured surrounding the system was _measured . The lens thickness (t) in the area exposed to the test was measured by measuring about 10 locations using a Mitotoya micrometer VL-50 or similar instrument and averaging the measurements. A DK1000 instrument was used to measure the oxygen concentration in the nitrogen stream (ie, oxygen that diffuses through the lens). The apparent oxygen permeability Dk _app of the lens material was determined from the following equation.
Dk _app = Jt / (P _oxygen )
Where J = oxygen flux [microliter O ₂ / cm ² -min],
P _oxygen = (P _measured −P _water vapor) = (% O _{2 in the} air stream) [mm Hg] = the partial pressure of oxygen in the air stream,
P _measured = atmospheric pressure (mm Hg),
P _water vapor = 0 mm Hg (in dry cell) at 34 ° C (mm Hg)
P _water vapor = 40 mm Hg (in wet cell) at 34 ° C (mm Hg)
t = average lens thickness (mm) in the exposure test area;
Dk _app is indicated in units of barrer.

The apparent oxygen permeability (Dk / t) of the material can be calculated by dividing the apparent oxygen permeability (Dk _app ) by the average lens thickness (t).

The above measurements are not corrected for the so-called boundary layer effect due to the use of water or saline baths on contact lenses during oxygen flow rate measurements. Boundary layer effect is lower than the actual intrinsic Dk value reported values for the apparent Dk silicone hydrogel material _{(Dk app) (Dk i)} . Furthermore, the relative influence of the boundary layer effect is greater for thinner lenses than for thicker lenses. The net effect is that the reported Dk appears to change as a function of lens thickness when it should remain constant.

  The intrinsic Dk value of the lens can be estimated based on the corrected Dk value for the surface resistance to the oxygen flow rate caused by the boundary layer as follows.

  Using the same equipment, calculate the apparent oxygen permeability value (single point) of Iotrafilcon A (Focus (registered trademark) N & D (registered trademark) of CIBA VISION CORPORATION) or Iotrafilcon B (AirOptix (trademark) of CIBA VISION CORPORATION). Measured. The reference lens had the same optical power as the test lens and was measured simultaneously with the test lens.

Using the same instrument, according to the above procedure for apparent Dk measurement, measure the oxygen flow rate through a series of thicknesses of the Iotrafilcon A or Iotrafilcon B (reference) lens to determine the intrinsic Dk value of the reference lens (Dk _i ) got. The series of thicknesses should cover a thickness range of about 100 μm or more. Preferably, the reference lens thickness range surrounds the test lens thickness. The Dk _{app for} these reference lenses should be measured with the same instrument as the test lens, and ideally should be measured at the same time as the test lens. Instrument setup and measurement parameters should be kept constant throughout the experiment. If desired, individual samples may be measured multiple times.

From the reference lens result, the residual oxygen resistance value R _r is determined using Equation 1 for calculation.

In the formula, t is the thickness of the reference lens to be measured, and n is the number of reference lenses to be measured. The residual oxygen resistance value R _r is plotted against t data and a curve of the form Y = a + bX is fitted. For the jth lens, Y _j = (ΔP / J) _j and X = t _j . The residual oxygen resistance value R _r is equal to a.

The correct oxygen permeability Dk _c (estimated intrinsic Dk) for the test lens is calculated based on Equation 2 using the residual oxygen resistance value determined as described above.
_{Dk c = t / [(t} / Dk a) -R r] (2)

Using the estimated intrinsic Dk of the test lens, based on Equation 3, the apparent Dk ( _{Dka_std} ) that would be obtained for a standard thickness lens in the same test environment can be calculated.
_{Dka_std} = t _std / [(t _std / Dk _c ) + R _{r_std} ] (3)

Ion permeability measurement The ion permeability of the lens was measured according to the procedure described in US Pat. No. 5,760,100 (incorporated herein by reference in its entirety). The ion permeability values reported in the following examples are the relative ionoflux diffusion coefficients (D / D _ref ) for the lens material Alsacon as a reference material. Alsacon has an ionoflux diffusion coefficient of 0.314 × 10 ⁻³ mm ² / min.

Water contact angle (WCA) measurement Water contact angle (WCA) measurement is a droplet method using a DSA 10 drop shape analysis system from Kruss GmbH, Germany with pure water (Fluka, surface tension 72.5 mN / m at 20 ° C). Carried out by. For measurement, the contact lens was removed from the storage solution with tweezers and the excess storage solution was removed by gently shaking. The contact lens was placed on the male part of the lens mold, and the moisture was gently wiped with a clean dry cloth. Next, a water droplet (about 1 μl) was metered into the top of the lens, and the temporal change (WCA (t), circle fitting mode) of the contact angle of this water droplet was monitored. WCA was calculated by extrapolation of graph WCA (t) up to t = 0.

UV Absorbance Contact lenses were manually placed in a specially manufactured sample holder or the like that can maintain the shape of the lens as it was in the eye. Next, the holder was immersed in a quartz cell having a path length of 1 cm containing phosphate buffered saline (PBS, pH of about 7.0 to 7.4) as a reference. In this measurement, a visible ultraviolet spectrophotometer such as a Varian Cary 3E visible ultraviolet spectrophotometer can be used together with a Lablab DRA-CA-302 beam splitter or the like. % Transmission spectra were collected in the 250-800 nm wavelength range and% T values were collected at 0.5 nm intervals. This data was transferred to an Excel spreadsheet and used to determine if the lens was compatible with class 1 UV absorbance. The UV absorbance was calculated using the following formula:

  Where luminescence% T is the average% transmission between 380 and 780.

Example 2
This example illustrates one general procedure for synthesizing crosslinkers according to Scheme 1 shown below (in Scheme 1,

Are polydimethylsiloxane segments and hydrophilic polymer chains (eg, polyethylene glycol, PEG, respectively)). It will be appreciated that various techniques known to those skilled in the art can be used to prepare the crosslinkers of the present invention.

PEG monoethyl ether (Aldrich, 202509), acryloyl chloride (Aldrich, A24109), triethylamine, N (Et) ₃ (Acros, 219510500), 1-thioglycerol (Fluke, 88639), α, ω-diaminopropyl terminated poly Dimethylsiloxane (Shin Etsu, KF-8012) and isophorone diisocyanate IPDI (Aldrich, 317684) were purchased from the vendor specified in brackets.

Acrylation of PEG monomethyl ether (2) 256.67 g (0.128 mol) of PEG monomethyl ether (1) was dissolved in 750 ml of anhydrous methylene chloride and 37.7 g (0.373 mol) of triethylamine was added to the reaction mixture. Freezing, pumping and thawing steps (freeze the reaction mixture in liquid nitrogen in a flask, evacuate under vacuum for 5 minutes, stop the vacuum and thaw the reaction mixture by immersing the flask in warm water) 3 times After repetition, a stream of nitrogen gas was passed through the flask and a catalytic amount of DMAP (4-dimethylaminopyridine) was added. The clear reaction mixture was cooled to 0 ° C. and kept under nitrogen gas. 58 g (0.64 mol) of acryloyl chloride was diluted with an equivalent amount of dry methylene chloride and then added to the reaction mixture via syringe over 1 hour. The reaction mixture turned yellow with the addition of acryloyl chloride. The reaction was then gradually warmed to room temperature and stirred overnight. The next day, the reaction mixture was quenched with 200 ml of water and the solvent was removed on a rotary evaporator. The product, an off-white solid, was dissolved in 2 L of water, filtered and purified by aqueous ultrafiltration. After lyophilization on a plate dryer, 18 g (36%) of a colorless powder was collected.

Synthesis of Compound (3) 2 60.92 g (0.029 mol) prepared above was dissolved in 600 ml of THF at 35 ° C. in a 1 L three-necked flask and stirred under nitrogen. 7.48 g (0.069 mol) of 1-thioglycerol was added to the reaction mixture. Thereafter, 15 ml of a 1N KOH solution in 1-propanol was added. The reaction mixture was stirred at 35 ° C. for 2-3 hours and monitored for reaction completion by thiol titration. After completion of the reaction, the reaction mixture was acidified by adding 1N HCl. After 1 L of water was added to the reaction mixture, the solvent was removed under reduced pressure. The product was then purified by ultrafiltration and lyophilized. 45.7 g (68%) of a colorless solid was collected.

Synthesis of Compound (4) 5.02 g (2.28 mol) of PEG glycerol (3) and 1.22 g (5.53 mmol) of isophorone diisocyanate (IPDI) were dissolved in 40 ml of MEK in a two-necked flask, Flushed for minutes and added 3 drops of dibutyltin dilaurate (DBTDL) catalyst to the mixture and stirred overnight at 35 ° C. under nitrogen atmosphere. The next day, 24.04 g (5.34 mmol) of KF-8012 was added to the reaction pot for further reaction to form a bifunctional hydrophilized PDMS crosslinker. The reaction was stirred at 38 ° C. overnight. The next day, the reaction was stopped and the solvent was removed under reduced pressure. The crude product, an off-white oily paste, was triturated in n-hexane, filtered and dried. 27.8 g (89%) of an off-white solid was collected.

Synthesis of crosslinker (5) 4 22.00 g (1.913 mmol) were acrylated as described above for 2 and purified in different ways. The crude product in CH ₂ Cl ₂ was extracted with water (2 × 200 ml). The organic layers were combined, dried over MgSO ₄ , filtered and the solvent removed under reduced pressure. 19.09 g (96%) of an off-white paste was collected.

Product analysis The product was analyzed by 1H NMR and GPC. GPC data shows that the molecular weight of diamino PDMS has doubled due to the formation of urea linkages with IPDI to form product 4, but the molecular weight of acrylated product 5 remains the same.

Example 3
This example shows the synthesis of a polydimethylsiloxane crosslinker that uses a variety of hydrophilic and hydrophobic groups and molecular weights as starting materials to form many different structures. The resulting hydrophilized PDMS crosslinker was included in the formulation to achieve a self-wetting lens surface with acceptable lens properties. Following the procedure described in Example 2, various crosslinkers were prepared from various combinations of hydrophilic components, IPDI and PDMS as shown in Scheme 2.

A Michael addition between PEG acrylate (molecular weight 2000) and thioglycerol in 1-PrOH was performed and a colorless product was achieved with 100% conversion. The product was analyzed by 1N NMR. PEG thioglycerol (molecular weight 2000) was reacted with IPDI and PDMS diamine / diol with molecular weight 3000 and / or 4500 in MEK under N ₂ atmosphere. The product was acrylated in CH ₂ Cl ₂ .

  The PDMS cross-linking agents prepared above were blended alone (macromer) or in combination with a vinyl monomer to form two types of lens formulations (ie, polymerizable compositions) as shown in Table 1.

  Contact lenses were made by one casting of the previously prepared lens formulation using one of double-sided molding (DSM) or LIGHTSTREAM ™ (LS) technology.

  DSM or LS lenses were made from these formulations. The lens was easily removed from the mold and extracted in ethanol, but was not subjected to surface treatment after curing.

From the lens formulation prepared as described above, it is reusable similar to the mold shown in FIGS. 1-6 and 7,387,759 of US Pat. No. 7,384,590 (FIGS. 1-6). LS lenses were prepared by casting in a mold. The mold included a female half made of CaF ₂ and a male half made of PMMA. The UV irradiation light source was a Hamamatsu lamp with a 380 nm cut-off filter with an intensity of about 4.6 mW / cm ² . The lens formulation in the mold was irradiated with UV light for about 30 seconds. The cast molded lens was extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed with water, hydrated and packaged / autoclaved into a lens package containing phosphate buffered saline.

A DSM lens was prepared as follows. Approximately 75 microliters of the lens formulation prepared as described above was filled into a female part of a polypropylene lens mold, and the mold was closed by a male part (base curve mold) of the polypropylene lens mold. Contact lenses were obtained by curing the closed mold for about 5 minutes with a UV irradiation light source (Hamamatsu lamp with a 380 nm cut-off filter with an intensity of about 16 mW / cm ² ). The cast molded lens was extracted with isopropanol or methyl ethyl ketone (MEK), rinsed with water, hydrated and packaged / autoclaved in a lens package containing phosphate buffered saline.

Photorheology was tested by using a Hamamatsu lamp with a stack of 330 nm and 388 nm long pass cutoff filters placed just in front of the sample. The strength (approximately 4 mW / cm ² ) was measured by using an IL1700 detector using a SED005 sensor with an International light 297 nm cutoff filter, and a long pass filter was placed before the formulation was cured. The results of the photorheological test are reported in Table 2.

  Uncoated lenses do not adhere to each other or to containers (glass vials or polypropylene cups). Such lenses are slippery and sink in the water. Further, as shown in Table 2, the lens was evaluated by measuring the contact angle of the droplet method. Most lenses are clear but slightly yellowish and brittle.

Example 4
This example illustrates a method for preparing chain extended PDMS crosslinkers with pendant polyethylene glycol (PEG) chains.

Intermediate Copolymer Synthesis 20.58 g (10.29 mmol) monoamino-terminated Jeffamine (polyethylene glycol-NH ₂ , molecular weight 2000 Dalton) solution in 40 ml THF is added by a dropping funnel to 10.000 g (10.29 mmol) in 500 g THF (tetrahydrofuran). The stepwise reaction was initiated by adding to the cooled Vestanat solution over about 30 minutes. After the mixture was stirred at 0 ° C. for about 30 minutes, the reaction mixture was allowed to come to room temperature and stirred for another about 2 hours. A solution of 69.98 g (15.55 mmol) diaminopropyl terminated polydimethylsiloxane (KF-8012, molecular weight 4500 daltons) in 40 ml THF was prepared in a separate flask and cooled to 0 ° C. in an ice bath. The Jefamine / Vestanat portion was added to the PDMS solution in the ice bath over about 30 minutes via a dropping funnel. The mixture was stirred in an ice bath for about 30 minutes and then at room temperature (RT) for an additional about 2 hours. 300 ml of isopropyl alcohol (IPA) was added to the reaction mixture and THF was removed under reduced pressure on a rotary evaporator, after which 1000 ml of water was slowly added and finally IPA was removed. An intermediate copolymer with two terminal amino groups and a pendant PEG chain was obtained and used immediately in the acrylate reaction.

Acrylation of amino-terminated intermediate copolymer Acrylation reaction of amino-terminated intermediate copolymer was carried out in an aqueous environment under basic conditions. Solvent exchange copolymer (1000 ml) was charged to a cooled (0 ° C.) reactor equipped with a stir bar, thermometer and aqueous pH probe. The rebellious mixture was mixed at 300 rpm. In a separate glass beaker, the required amount of sodium bicarbonate (determined based on the determined amino content of the intermediate copolymer) was dissolved in deionized water and slowly added to the reactor. Additional water may be required to ensure that the pH probe is immersed in the reaction solution. A Metrohm automatic titrator and pH probe were connected. A reservoir containing 20% NaOH solution was inserted into the titrator and a solution distribution tube was placed in the reactor. Once the thermometer showed that the reaction solution temperature was 0 ° C., the titrator was set up and 20% NaOH was dispensed into the mixture until the reaction pH reached 9.5. The required amount (determined based on the determined amino content of the intermediate copolymer) of acryloyl chloride was then dispensed into the Hamilton airtight syringe and the extension tube was attached to the syringe and placed in the reactor. The syringe should be placed in an automatic dispensing module and programmed to add the entire amount of acryloyl chloride at a constant rate over 120 minutes. During the addition of acryloyl chloride, an automatic titrator metering of 20% NaOH solution was maintained to maintain the reaction pH at 9.5. Once the acryloyl chloride addition was complete, the temperature was maintained and the reaction mixture was stirred for an additional 60 minutes. After further mixing time, the temperature was raised to 25 ° C. Once the desired temperature was reached, the NaOH reservoir was removed and a reservoir containing 2N HCl was inserted. A distribution tube was placed in the reactor and the titrator was programmed to dispense acid until the pH of the reaction was 7.0. The reaction mixture was stirred for an additional 30 minutes. Once the reaction was complete; the solution was withdrawn from the reactor and filtered through an intermediate fritted glass funnel to remove particles. Purification was performed by ultrafiltration using a 5K membrane. The ultrafiltered material was lyophilized on a lyophilizer.

  As shown in Table 3, from Jeffamine 2000, Vestanat (isophorone diisocyanate, trimer) and PDMS (molecular weight 4500 and 3000 Daltons), various proportions of hydrophilic and hydrophobic components, pendant linear A crosslinking agent having a Jeffamine chain was prepared.

Example 5
Contact lenses were prepared by casting a lens formulation (Formulation I) containing a crosslinker prepared in Example 4 according to the procedure described in Example 3. The lens properties of the lens formulation and contact lenses prepared therefrom are reported in Table 4.

  Dissolving the cross-linking agent, N, N-dimethylacrylamide (DMA), N- [Tris (trimethylsiloxy) silylpropyl] acrylamide (ShinEtsu's TRIS-Am, # 805001) prepared in Example 4 in 1-propanol. The five lens formulations having the compositions shown in Table 5 were prepared. All formulations were clear.

  The lens properties of the lens formulations and contact lenses prepared therefrom are reported in Table 6. However, after autoclaving, the lens became cloudy.

Example 6
This example shows how to prepare a chain extended PDMS crosslinker with pendant 3-armed hydrophilic polymer chains according to a stepwise reaction process.

Monoamino-terminated hydrophilic polymer with three PEG arms

A monoamino-terminated 3-armed hydrophilic polymer having the following structure was prepared as follows. A solution of 30 g (28.41 mmol) Vestanat was prepared in 400 ml THF and cooled to 0 ° C. Monoamino-terminated Jeffamine M2070 113.64 g (56.82 mmol) was dissolved in 40 ml THF and added to the stirring Vestanat solution over 30 minutes via a dropping funnel. The reaction temperature was maintained during Jeffamine addition and for an additional hour. The reaction mixture was stirred at room temperature for an additional hour. In another flask, a diamine functional 56.80 g (28.40 mmol) Jeffamine ED2003 (polyethylene glycol diamine, molecular weight 2000 Dalton) solution was prepared in 40 ml THF and cooled to 0 ° C. The Jeffamine M2070 / Vestanat reaction mixture was added to the ED2003 solution via an addition funnel at 0 ° C. over 30 minutes. The reaction mixture was stirred at 0 ° C. for 1 hour after the addition and then at room temperature for an additional hour. Following the solvent exchange step described above, the material was purified by ultrafiltration using a 3K membrane and lyophilized.

Monoamino-terminated polymer with one PVP arm and two PEG arms According to the above procedure for preparing 3PEG arm polymer

A monoamino-terminated 3-armed hydrophilic polymer having the structure: In addition, after water ultrafiltration, the material was purified again by removing non-functional (dimerized) branched Jeffamine / pyrrolidone using ceramic ultrafiltration (5K).

Intermediate Copolymer Synthesis An intermediate copolymer having a PDMS segment and a pendant three-armed hydrophilic polymer chain was prepared from the monoamino terminated 3-arm polymer prepared above according to the procedure described in Example 4. Diamino terminated PDMS (molecular weight 4500 Dalton) was used for the preparation.

Acrylation of the intermediate copolymer Acrylation of the diamino-terminated intermediate copolymer was performed according to the procedure described in Example 4.

Example 7
Two crosslinkers (crosslinkers 5 and 6) were prepared according to the procedure described in Example 6. They had the composition and structure shown in Table 7.

  The prepared crosslinker was formulated in 1-propanol with Darocure 1173 alone and with monomers (combination of DMA, TRIS, PEG acrylate and MBA). Formulation composition, photorheology and lens property data are shown in Table 8. Crosslinkers with branched hydrophilic components showed increased wettability compared to other hydrophilic components, Formulation VI showed a 71 ° contact angle, and lens properties were acceptable. . Both monomers and single formulations of these crosslinkers showed very high viscosities (10000-42000 mPasec) in the 60-75% solids region.

Example 8
A: Chain extended PDMS crosslinker with pendant p (DMA) chain By radical polymerization using 3-mercapto-1,2-propanediol as a chain transfer reagent, monodihydroxyl terminated poly ( N, N-dimethylacrylamide) (poly (DMA)) was prepared.

In a general experiment, DMA (15.861 g, 160 mmol), AIBN (0.263 g, monomer 1.44 wt%), 3-mercapto-1,2-propanediol (2.388 g, 22.08 mmol) and toluene. (42.80 ml) was introduced into a 250 ml Pyrex round bottom flask. The solution was purged with N ₂ gas for 30 minutes and then polymerized at 65 ° C. for 12 hours. The product was dialyzed for 12 hours using a cellulose ester (Spectra / Por® Biotec) tube of MWCO 500 in 2 L toluene. The final product was precipitated into ethyl ether, decanted and dried under vacuum. The number average molecular weight of the final polymer was 383 g / mol based on GPC using THF as the eluent and polystyrene as the standard.

  Monobishydroxyl terminated poly (DMA) prepared above in the presence of 1,6-hexamethylene diisocyanate (2.51 g) and catalytic amount of dibutyltin dilaurate (DBTDL) (0.075%) in 14 g of toluene ( 4.50 g) and dihydroxyl-terminated PDMS (7.00 g) with a PDMS segment and pendant poly (DMA) chain and terminated with an isocyanate group by condensation reaction at 40 ° C. for 2 hours An intermediate copolymer was synthesized. The reaction was allowed to proceed until the titration NCO ratio approached the theoretical prediction.

  In the second step, the isocyanate-terminated intermediate copolymer was then converted to a crosslinker by reacting with N-hydroxyethylacrylamide (HEAA) (0.69 g) at room temperature for 5-6 hours. The resulting crosslinker was dialyzed using a regenerator cellulose tube of MWCO 3,500 in methanol and then in ethyl acetate. The final crosslinker was maintained in solution with OH-TEMPO inhibitor (100 ppm relative to polymer). The number average molecular weight of the final polymer was 7,160 g / mol based on GPC using THF as eluent and polydimethylsiloxane as standard.

B: Chain-extended PDMS crosslinker with pendant p (DMA) chain 44.46 g (448.0 mmol) DMA, 0.184 g (1.12 mmol) AIBN, 6.726 g (61.82 mmol) 3-mercapto-1,2-propanediol ), 102.6 g of toluene and 10.29 g of ethyl acetate were introduced into a 250 ml round bottom flask. After degassing by nitrogen bubbling for 1.0 hour, polymerization was carried out at 55 ° C. for 12 hours. The product was dialyzed for 12 hours using a cellulose ester (Spectra / Por® Biotec) tube of MWCO 500 in toluene. The final product was precipitated into hexane, decanted and dried under vacuum. The number average molecular weight of the final polymer was 541 g / mol based on GPC using THF as the eluent and polystyrene as the standard.

  To a dry 250 ml flask was added 28.0 g (29.3 mmol) purified Shin-Etsu 160AS, 24.0 g (29.0 mmol) monodihydroxyl-terminated poly (DMA) prepared above and 64.0 g toluene. . The flask was placed in a 40 ° C. oil bath and stirred until dissolved. After cooling to room temperature, 11.81 g (69.88 mmol) of hexamethylene diisocyanate was added along with 3 drops of dibutyltin dilaurate (DBTDL). The reaction was allowed to proceed for about 2 hours in a 40 ° C. oil bath and the NCO conversion was monitored by titration until it was close to the theoretical value. After cooling to room temperature again, 3.256 g (27.95 mmol) of HEAA was added along with 3 drops of catalyst and allowed to react overnight. The product was dialyzed using regenerator cellulose tubes of MWCO 3,500 in methanol and ethyl acetate, respectively. The final macromer was kept in solution with the H-TEMPO inhibitor in preparation for solids measurement, formulation and lens manufacturing. The number average molecular weight of the final polymer was 7,464 g / mol based on GPC using THF as the eluent and polydimethylsiloxane as the standard.

C. Formulation and Lens Casting Formulations were prepared by dissolving a chain extended PDMS crosslinker with pendant p (DMA) chains in dipropylene glycol methyl ether (DPGME) to a concentration of about 60% by weight. Each formulation also contained 0.3% by weight of Irgacure 2959. Typical conditions for photorheology and lens production were 4-6 mW / cm ² , about 4-10 seconds with a 297 nm filter cutoff, depending on the mold type used. The molded lenses are characterized and their properties are reported in Table 9.

D: Mold cleaning All the above formulations were used for mold cleaning experiments. After manufacturing the lens using a quartz mold, the mold was rinsed with tap water. The mold was then inspected with an OptiSpec microscope. In most cases, the mold was efficiently cleaned.

Example 9
The 1 liter reaction vessel was evacuated overnight to remove moisture and the vacuum was released with dry nitrogen. The reactor was charged with 73.59 g (75 meq) of dry X-22-160AS (α, ω-bis (2-hydroxyethoxypropyl) polydimethylsiloxane, molecular weight about 1000, Shin-Etsu) and then just distilled. About 26.68 g (120 meq) of isophorone diisocyanate (IPDI) was added to the reactor. After purging the reactor with nitrogen and heating to 45 ° C. with stirring, about 0.30 g of dibutyltin dilaurate (DBTDL) was added. The reactor was sealed and a positive nitrogen flow rate was maintained. An exotherm occurred, after which the reaction mixture was cooled and stirred at 55 ° C. for 2 hours. About 23.89 g (21.96 meq) of dried Ymer ™ N120 (mono-3,3-bis (hydroxymethyl) butyl and monomethoxy terminated polyethylene glycol, molecular weight about 1000, Perstorp Polyols, Inc.) Added to the reactor at 55 ° C., followed by 100 μl of DBTDL. After continuing the reaction for 2 hours, the heating was stopped and the reactor was cooled. Approximately 6.59 g (50.64 meq) of 2-hydroxyethyl methacrylate (HEMA) was added to the reactor along with 100 μl of DBTDL. When the reaction is continued for 24 hours under dry air with gentle stirring,

Wherein G ₀ and G ₄ are —C (O) —O—C ₂ H ₄ —O—C (O) —NH—Z ₃ —NH—C (O) —O— and —O, respectively. —C (O) —NH—Z ₃ —NH—C (O) —O—C ₂ H ₄ —O—C (O) —, wherein Z ₃ is

D ₀ , D ₁ and D ₂ are

And G ₁ , G ₁ ′, G ₂ , G ₂ ′ and G ₅ are independently of each other —O—C (O) —NH—Z ₃ —NH—C (O) — O—, Z ₃ is as defined above, A ₁ and A ₃ are —C ₂ H ₄ OC ₃ H ₆ —, and A ₂ and A ₄ are —C ₃ H ₆ OC ₂ H. ₄ -, m is about 15 to 29 integer, and m1 and m2, independently of one another, about 7 to about 14 integer, a1 is an integer of 0 to 9, .omega.1 and ω2 are Independent of each other, an integer of 0 to 10)
This led to the formation of a hydrophilized chain-extended polysiloxane cross-linking agent (YSX-75). The number average molecular weight of YSX-75 was determined to be about 17,000 daltons based on conventional GPC using DMF as the eluent and polystyrene as the standard. The product was decanted and stored under refrigeration.

Example 10
Copolymer / Macromer Synthesis A 500 ml jacketed reactor was equipped with a heating / cooling loop, a diaphragm inlet adapter, a reflux condenser with an N ₂ inlet adapter, a vacuum line and an overhead stirrer. After preparing 25.6 g of a hydrophilic chain-extending PDMS cross-linking agent (YSX-75 prepared in Example 9) as a 50% solution in t-amyl alcohol, the reaction vessel was charged. The solution was degassed under a vacuum of less than 1 mBar for 5 minutes and then pressurized again with dry nitrogen. This degassing procedure was repeated a total of 6 times.

  5.76 g of methylbis (trimethylsiloxy) silyl] propyl glycerol methacrylate (SiGMA), 1.50 g of methacrylic acid, 13.67 g of N, N-dimethylacrylamide and 1.23 g of aminopropylmethacrylamide hydrochloride with 1.23 g of deionized water A monomer solution was prepared by dissolving in a mixture with 175 g of t-amyl alcohol. The monomer solution was transferred to a further funnel placed above the reaction vessel and then degassed for 10 minutes under a vacuum of 100 mBar and then repressurized with dry nitrogen. This degassing procedure was repeated a total of 3 times.

  Mix 0.15 g azobis (isobutyronitrile) pre-dissolved in 37.50 g t-amyl alcohol with 0.755 g cysteamine hydrochloride pre-dissolved in 0.60 g deionized water and 1.80 g methanol. An initiator and chain transfer agent (CTA) pot solution was prepared by degassing under vacuum of 100 mBar for 10 minutes and then pressurizing again with dry nitrogen. This degassing procedure was repeated a total of 3 times.

  A CTA feed solution was prepared by dissolving 1.136 g of cysteamine hydrochloride in 0.90 g of deionized water, 2.25 g of methanol and 56.25 g of t-amyl alcohol.

After degassing both the YSX-75 solution and the monomer solution, the monomer solution was charged into the reaction vessel. Next, the temperature of the mixed solution was quickly raised from room temperature to 64 ° C. When the temperature approached 64 ° C., the initiator / CTA solution was injected into the system and the CTA feed solution was fed through a combination of degassing unit and HPLC pump for 2 hours. The reaction mixture was maintained at 64 ° C. under nitrogen for 5 hours before injecting the initiator solution. After the copolymerization was completed and the temperature was cooled to room temperature, the reaction solvent was changed to isopropyl alcohol, and then changed to water to make a 2 liter solution. The copolymer solution was purified by ultrafiltration and then charged to a 2 L reactor equipped with an overhead stirrer, refrigeration loop, thermometer and Metrohm Model 718 STAT Titrino pH meter and dispensing tip. The reaction mixture was then cooled to 1 ° C. 4.8 g of NaHCO ₃ was charged into the solution and dissolved by stirring. Titrino was set to maintain the pH at 9.5 by intermittent addition of 20% sodium hydroxide solution. Then, using a syringe pump, 9.6 ml of acryloyl chloride was added over 2 hours. After the solution was stirred for an additional hour, Titrino was set to neutralize the reaction mixture by the addition of 2N hydrochloric acid. The macromer solution was then filtered and purified by ultrafiltration until the permeability conductivity was less than 5 μS / cm. The purified macromer solution was then solvent-exchanged with 1-propanol to obtain a stock solution.

Formulation composition and photorheology

Lens manufacture Lenses were manufactured in a polypropylene lens mold using UV energy provided by photorheology. The lens was demolded in deionized water, packaged in a saline solution, and then autoclaved at 121 ° C. for 30 minutes.

Lens characteristics

Example 11
Copolymer / Macromer Synthesis Copolymers and macromers were prepared in the same manner as the macromer of Example 10 except that aminopropyl methacrylamide hydrochloride was not used as one of the monomers.

Formulation composition and photorheology

Lens Production A lens was produced according to the procedure described in Example 10.

Lens characteristics

Example 12
The 1 liter reaction vessel was evacuated overnight to remove moisture and the vacuum was released with dry nitrogen. The reactor was charged with 73.59 g (75 meq) of dry X-22-160AS (α, ω-bis (2-hydroxyethoxypropyl) polydimethylsiloxane, molecular weight about 1000, Shin-Etsu) and then just distilled. About 39.23 g (176.5 meq) of isophorone diisocyanate (IPDI) was added to the reactor. After purging the reactor with nitrogen and heating to 45 ° C. with stirring, about 0.30 g of dibutyltin dilaurate (DBTDL) was added. The reactor was sealed and a positive nitrogen flow rate was maintained. An exotherm occurred, after which the reaction mixture was cooled and stirred at 55 ° C. for 2 hours. About 72.12 g (66.20 meq) of dry Ymer ™ N120 (mono-3,3-bis (hydroxymethyl) butyl and monomethoxy terminated polyethylene glycol, molecular weight about 1000, Perstorp Polyols, Inc.) Added to the reactor at 55 ° C., followed by 100 μl of DBTDL. After continuing the reaction for 8 hours, heating was stopped and the reactor was allowed to cool overnight. Nitrogen bubbling was stopped and the reactor was filled with dry air with gentle stirring. An α, ω-bis (isocyanate) terminated chain-extended polysiloxane with multiple polysiloxane segments and pendant PEG 1000 chains was formed. About 9.83 g (75 meq) of 2-hydroxyethyl methacrylate (HEMA) was added to the reactor along with 100 μl of DBTDL. When the reaction is continued for 24 hours under dry air with gentle stirring,

Wherein G ₀ and G ₄ are —C (O) —O—C ₂ H ₄ —O—C (O) —NH—Z ₃ —NH—C (O) —O— and —O, respectively. —C (O) —NH—Z ₃ —NH—C (O) —O—C ₂ H ₄ —O—C (O) —, wherein Z ₃ is

G ₁ ′, G ₂ , G ₂ ′ and G ₃ are independently of each other, —O—C (O) —NH—Z ₃ —NH—C (O) —O—. And Z ₃ is as defined above, and D ₁ and D ₂ are

Ν2 is an integer of 1 or 2, ω2 is an integer of 0 to about 10, υ1 and ω3 are each independently an integer of 0, 1 or 2, and m is (It is an integer of about 15 to 29, and m1 is an integer of about 7 to about 14.)
A hydrophilized chain-extended polysiloxane crosslinking agent (YMER50X) represented by The number average molecular weight of YMER50X was determined to be about 12,000 daltons based on conventional GPC using DMF as the eluent and polystyrene as the standard. The product was decanted and stored under refrigeration.

Claims (14)

Formula (I)

[Where:
D ₀ , D ₁ , D ₂ and D ₃ are each independently of the formula (II)

{Wherein G ₅ is as defined below, and A ₁ , A ₂ , A ₃ and A ₄ are each independently a direct bond, linear or branched C ₁ -C ₁₀ alkylene. A divalent group, — (CH (R ″) CH ₂ O) _r1 —CH (R ″) CH ₂ — (wherein R ″ is H or methyl, and r1 is an integer of 1 to 20) or C _{1 to} C ₇ alkyleneoxy is a C _{1 to} C ₇ alkylene divalent group, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₁ ′, R ₂ ′, R ₃ ′, R ₄ ′, R ₅ ′, R ₆ ′, R ₇ ′ and R ₈ ′ are independently of each other C ₁ -C ₈ alkyl, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy. Phenyl, fluoro (C ₁ -C ₁₈ alkyl), —alk- (OCH ₂ CH ₂ ) _n —OR ₉ (wherein “alk” is a C ₁ -C ₆ alkylene divalent group, R ₉ C ₁ -C ₆ alkyl And n is an integer of 1 to 20, a1 is an integer of 0 to 8, m1, m2, p1 and p2 are each independently an integer of 0 to 150, and (m1 + p1 ) And (m2 + p2) are independently 2 to 150}
A divalent group of
e1, e2, t1, t2 and t3 are each independently an integer of 0 or 1;
υ1, υ2 and υ3 are independently an integer from 0 to 5, provided that (υ1 + υ2 + υ3) ≧ 1;
ω1, ω2, and ω3 are each independently an integer of 0-20, where (ω1 + ω2 + ω3) is an integer of 1-20;
L ₁ , L ₂ and L ₃ are each independently a direct bond,

Where R ₁₂ is hydrogen or C ₁ -C ₄ alkyl;
L ₁ ′, L ₂ ′ and L ₃ ′ are independent from each other,

Where R ₁₂ is as defined above, Y is —O— or —NR′—, where R ′ is hydrogen or C ₁ -C ₈ alkyl, and Y Is bound to T ₁ , T ₂ or T ₃ ;
G _O , G ₁ , G ₁ ′, G ₁ ″, G ₂ , G ₂ ′, G ₂ ″, G ₃ , G ₃ ′, G ₃ ″, G ₄ and G ₅ are directly coupled to each other independently. Or a divalent group of —Z ₁ —X ₁ —Z ₂ —X ₂ —Z ₃ —X ₃ —Z ₄ —, wherein X ₁ , X ₂ and X ₃ are each independently a direct bond , -O-, -NR'-, -C (O) -NR'-, -NR'-C (O)-, -O-C (O) -NH-, -NH-C (O) -O -, -NR'-C (O) -NH-, -NH-C (O) -NR'-, -S-, -C (O) -O-, -O-C (O)-, -NH —C (O) —NH—Z ₀ —NH—C (O) —NH—, —O—C (O) —NH—Z ₀ —NH—C (O) —O—, —O—C (O ) —NH—Z ₀ —NH—C (O) —NH— and —NH—C (O) —NH—Z ₀ —NH—C (O) —O— And Z ₀ is a linear or branched C _{2 to} C ₁₂ optionally containing one or more bonds of —O—, —NR′—, —S— and —C (O) —. An alkylene divalent group or a C ₅ -C ₄₅ alicyclic or aliphatic alicyclic divalent group, R ′ is H or C ₁ -C ₈ alkyl, Z ₁ , Z ₂ , Z ₃ and Z _4. Are each independently a direct bond, optionally a linear or branched C ₁ , containing one or more of —O—, —NR′—, —S— and —C (O) —. -C ₁₈ alkylene diradical, C ₁ -C ₇ alkyleneoxy C ₁ -C ₇ alkylene divalent radical, - (CH (R ") CH 2 O) r1 -CH (R") CH 2 - ( wherein, R "and r1 is a divalent radical of a is) as defined above, unsubstituted phenylene divalent radical, C ₁ -C ₄ alkyl or C ₁ -C ₄ phenylene divalent radical substituted with an alkoxy or ₇ -C ₁₂ Arakiren divalent radical, optionally -O -, - NR '-, - S- and -C (O) - of C ₅ -C ₄₅ cycloaliphatic or aliphatic including in one or more of the binding family alicyclic diradical, C ₆ -C be ₂₄ aromatic or araliphatic bivalent radical, or combinations thereof;
R ₁₀ and R ₁₁ are independently of each other hydrogen or C ₁ -C ₄ alkyl;

Is a linear or 3 containing at least about 60 wt% (preferably at least about 70 wt%, more preferably at least about 80 wt%, more preferably at least about 90 wt%) of one or more hydrophilic monomer units An arm-like (or Y-shaped) hydrophilic polymer chain; and T ₁ , T ₂ and T ₃ , independently of one another, are linear or branched C ₂ -C ₂₄ aliphatic trivalent groups, C ₅ -C ₃₀ cycloaliphatic or aliphatic cycloaliphatic ternary groups, one or more C ₄ -C ₃₀ aliphatic heterocyclic trivalent radical or a C ₃ containing an oxygen or nitrogen atom of the -C ₂₄ aromatic or araliphatic Is a trivalent group]
A chain-extended polysiloxane crosslinker represented by _{R 1, R 2, R 3} , R 4, R 5, R 6, R 7, R 8, R 1 ', R 2', R 3 ', R 4', R 5 ', R 6', R 7 The chain-extended polysiloxane crosslinker of claim 1 wherein 'and R ₈ ' are methyl. In the formula (I), t1, t2 and t3 are integers of 1, and the chain-extended polysiloxane crosslinking agent has the following steps:
(1)
(A) A mercaptan having a unique thiol group and two first reactive functional groups (other than a thiol group) is converted to a monoethylenically functionalized hydrophilic polymer (i.e., a unique polymer) under Michael addition or thiol-ene reaction conditions. A linear or three-armed hydrophilic polymer having a terminal ethylenically unsaturated group)
(B) Monothiol-terminated (linear or Y-shaped) hydrophilic polymer with two first reactive functional groups (other than ethylenically unsaturated groups) under Michael addition or thiol-ene reaction conditions Reacting with a vinyl-based monomer, or (c) a chain transfer agent (ie mercaptan) having only one thiol group and at least two first reactive functional groups, at least about 60 weights of one or more hydrophilic vinyl-based monomers % (Preferably at least about 70% by weight, more preferably at least about 80% by weight, even more preferably at least about 90% by weight) and one or more bulky vinylic monomers 0 to about 40% by weight (preferably 0 to about 30% by weight, more preferably from 0 to about 20% by weight, and even more preferably from 0 to about 10% by weight)
Obtaining a crosslinked linker having a pendant (straight or three-armed) hydrophilic polymer chain and two first reactive functional groups;
(2) at least one bifunctional having the crosslinking linker having a unique polysiloxane segment and two terminal second reactive functional groups under coupling reaction conditions in the presence or absence of a coupling agent; At least one dangling hydrophilic bonded to an organic bond that reacts with the polysiloxane to bond two terminal first or second reactive functional groups, at least two polysiloxane segments and a pair of adjacent polysiloxane segments. Forming an intermediate chain-extended polysiloxane polymer having a functional polymer chain; and (3) reacting with the first or second reactive functional group in the presence or absence of a coupling agent to form a covalent bond. An ethylenically functionalized vinyl system having a third reactive functional group (other than an ethylenically unsaturated group) capable of By using Nomar, said intermediate chain extension polysiloxane polymer and ethylenically functionalized, thereby obtained by a process comprising the step of forming a chain extension polysiloxane crosslinker,
The first reactive functional group is selected from the group consisting of amino (-NHR ', wherein R' is as defined above), hydroxyl, carboxyl and combinations thereof; The third reactive functional group is independently of each other hydroxyl group (—OH), amino group (—NHR ′), carboxyl group (—COOH), isocyanate group, epoxy group, aziridine group, azlactone group, acid chloride. And a chain-extended polysiloxane crosslinking agent according to claim 1 or 2, selected from the group consisting of: and combinations thereof. The mercaptan is mercaptoglycerol, 2-mercaptopyrimidine-4,6-diol; 4-amino-5-mercaptopentanoic acid, 2-mercapto-4-amino-6-hydroxypyrimidine, 2-mercaptosuccinic acid, 3-mercapto 2- (methylamino) propanoic acid, 2-mercapto-4,5-dihydro-1h-imidazole-4,5-diol, 3-mercaptotyramine, mercaptopropanediol, 2-mercaptomethylglutaric acid, 3-mercapto- Selected from the group consisting of DL-valine hydrochloride and combinations thereof;
The vinyl monomer having two first reactive functional groups is N, N-2- (meth) acrylamide glycolic acid, glycerol (meth) acrylate, 2-hydroxy-3-aminopropyl (meth) acrylate, 1 -From the group consisting of hydroxy-2-aminopropyl (meth) acrylate, 1-amino-2-hydroxypropyl (meth) acrylate, glutaconic acid, itaconic acid, citraconic acid, mesaconic acid, maleic acid, fumaric acid and combinations thereof Selected
The at least one difunctional polysiloxane is a polysiloxane terminated with diepoxypropoxypropyl, a polysiloxane terminated with dihydroxyethoxypropyl, a polysiloxane terminated with dihydroxyl (polyethyleneoxy) propyl, Carboxydecyl-terminated polysiloxane, dicarboxypropyl-terminated polysiloxane, dicaprolactam-terminated polysiloxane, di-N-ethylaminopropyl-terminated polysiloxane, diaminopropyl-terminated polysiloxane The chain-extended polysiloxane crosslinker of claim 3, selected from the group consisting of terminated polysiloxanes, polysiloxanes terminated with disuccinic anhydride, and combinations thereof. In the formula (I), t1, t2 and t3 are 0, and the chain-extended polysiloxane crosslinking agent has the following steps:
(1)
(It may be identical to each other, different also) (a) three first reactive functional group of C ₂ -C ₂₀ compound having, in the presence or absence of a coupling agent, the coupling reaction Under conditions, reacting with a hydrophilic polymer having only one second reactive functional group (linear or three-armed), or (b) C ₂ having three first reactive functional groups -C ₂₀ compound (reactive with organic bromides), organic bromides as ATRP initiators, at least about 60 wt% of one or more hydrophilic vinylic monomer (preferably at least about 70 wt%, more preferably at least about 80 0% to about 40% by weight (preferably 0 to about 30% by weight, more preferably 0 to about 20% by weight), more preferably at least about 90% by weight) and one or more bulky vinyl monomers. By reacting a mixture containing a polymerized ATRP polymer with a polymer containing ATRP polymer, as well as amino, hydroxyl, carboxyl, Obtaining a crosslinked linker having two first reactive functional groups selected from the group consisting of isocyanate groups and combinations thereof;
(2) at least one bifunctional having the crosslinking linker with a unique polysiloxane segment and two terminal third reactive functional groups under coupling reaction conditions in the presence or absence of a coupling agent At least one dangling hydrophilic bonded to an organic bond that reacts with a polysiloxane to bond two terminal first or third reactive functional groups, at least two polysiloxane segments and a pair of adjacent polysiloxane segments Forming an intermediate chain-extended polysiloxane polymer having a reactive polymer chain; and (3) reacting with the first or third reactive functional group to form a covalent bond in the presence or absence of a coupling agent. An ethylenically functionalized vinyl having a fourth reactive functional group (other than an ethylenically unsaturated group) that can be Obtained by a method comprising the step of ethylenically functionalizing said intermediate chain extended polysiloxane polymer by using a monomer, thereby forming a chain extended polysiloxane crosslinker, said second, third and second The four reactive functional groups are independently of each other a hydroxyl group (—OH), an amino group (—NHR ′), a carboxyl group (—COOH), an epoxy group, an isocyanate group, an azlactone group, an acid chloride, and combinations thereof. The chain-extended polysiloxane crosslinking agent according to claim 1 or 2, selected from the group consisting of: The ethylenically functionalized vinyl monomer is C ₂ -C ₆ hydroxylalkyl (meth) acrylate, C ₂ -C ₆ hydroxyalkyl (meth) acrylamide, allyl alcohol, allylamine, amino C ₂ -C ₆ alkyl (meth). acrylates, C ₁ -C ₆ alkylamino C ₂ -C ₆ alkyl (meth) acrylate, vinyl amine, amino C ₂ -C ₆ alkyl (meth) acrylamides, C ₁ -C ₆ alkylamino C ₂ -C ₆ alkyl (meth) acrylamide, acrylic acid, C ₁ -C ₄ alkyl acrylate (such as methacrylic acid, ethyl acrylate, propyl acrylate, butyl acrylate), N-[tris (hydroxymethyl) methyl] acrylamide, N, N-2-acrylamide Glycolic acid, β-methylacrylic acid (crotonic acid), α- Phenylacrylic acid, β-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic Acid, fumaric acid, 2- (1-aziridinyl) ethyl (meth) acrylate, 3- (1-aziridinyl) propyl (meth) acrylate, 4- (1-aziridinyl) butyl (meth) acrylate, 6- (1-aziridinyl) ) Hexyl (meth) acrylate, or 8- (1-aziridinyl) octyl (meth) acrylate, glycidyl (meth) acrylate, vinyl glycidyl ether, allyl glycidyl ether, (meth) acrylic acid halide group (—COX, X = Cl, Br or I), C ₁ ~C ₆ isocyanatomethyl al Kill (meth) acrylate, 2-vinyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-dimethyl-1,3-oxazolin-5-one, 2-vinyl -4-methyl-4-ethyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one, 2-vinyl-4,4- Dibutyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one, 2-isopropenyl-4,4-diphenyl-1,3- Oxazolin-5-one, 2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one, 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one, -Vinyl-4,4-diethyl-1,3-oxazolin-5-one, 2-vinyl-4-methyl-4-nonyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl- 4-phenyl-1,3-oxazolin-5-one, 2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, 2-vinyl-4,4-pentamethylene-1, 6. Chain extension according to claim 3, 4 or 5, selected from the group consisting of 3-oxazolin-5-one, 2-vinyl-4,4-dimethyl-1,3-oxazolin-6-one and combinations thereof. Polysiloxane crosslinking agent.
But ethylene oxide units, (meth) acrylamide units, C ₁ -C ₃ alkyl (meth) acrylamide units, di (C ₁ -C ₃ alkyl) (meth) acrylamide units, N- vinyl pyrrole units, N- vinyl-2 pyrrolidone units, 2-vinyl oxazoline units, 4-vinylpyridine units, mono C ₁ -C ₄ alkoxy having a molecular weight of 600 daltons, mono (meth) acryloyl at the end stop polyethylene glycol units, di (C ₁ -C ₃ alkylamino) (C ₂ -C ₄ alkyl) (meth) acrylate units, N-C ₁ ~C ₄ alkyl-3-methylene-2-pyrrolidone units, N-C ₁ ~C ₄ alkyl-5-methylene -2 - pyrrolidone units, N- vinyl C ₁ -C ₆ alkyl amide units, N- vinyl -N-C ₁ ~C ₆ alkyl amide units and its A linear chain comprising at least about 60 wt% (preferably at least about 70 wt%, more preferably at least about 80 wt%, even more preferably at least about 90 wt%) of one or more hydrophilic monomer units comprising these combinations Or the chain extension polysiloxane crosslinking agent of any one of Claims 1-6 which is a 3 arm-like (or Y-shaped) hydrophilic polymer chain.
The chain-extending polysiloxane cross-linking agent according to claim 7, wherein is a linear or three-armed (or Y-shaped) hydrophilic polymer chain containing a bulky vinyl monomer unit.
The chain extended polysiloxane crosslinking agent according to any one of claims 1 to 8, wherein is a linear hydrophilic polymer chain.
The chain-extended polysiloxane crosslinking agent according to any one of claims 1 to 8, wherein is a three-armed (or Y-shaped) hydrophilic polymer chain. (1) A crosslinking unit derived from at least one chain-extended polysiloxane crosslinking agent according to any one of claims 1 to 10;
(2) a hydrophilic unit derived from at least one hydrophilic vinyl monomer and at least two ethylenically unsaturated groups;
(3) optionally a hydrophobic unit derived from a hydrophobic vinyl-based monomer; and (4) a soluble amphiphilic prepolymer optionally comprising a UV absorbing unit derived from a polymerizable UV absorber.   First, (a) having at least one chain-extended polysiloxane cross-linking agent, (b) having at least one hydrophilic vinyl monomer, and (c) a fourth reactive functional group (other than a thiol group) or not A vinyl-based monomer having a chain transfer agent and / or a fifth reactive functional group (other than an ethylenically unsaturated group), (d) optionally a hydrophobic vinyl-based monomer, and (e) optionally polymerizable UV In a coupling reaction in the presence or absence of a coupling agent, a polymerizable composition comprising an absorbent is polymerized to form an intermediate copolymer and then reacted with the first or second reactive functional group. The intermediate copolymer is ethylenically functionalized with an ethylenically functionalized vinyl monomer having a sixth reactive functional group capable of forming a bond to form a prepolymer. Wherein the fourth, fifth and sixth reactive functional groups are, independently of one another, an amino group —NHR ′ (where R ′ is as defined above), hydroxyl 12. The prepolymer according to claim 11, wherein the prepolymer is selected from the group consisting of a group, a carboxyl group, an acid halide group, an azlactone group, an isocyanate group, an epoxy group, an aziridine group, and combinations thereof.   First, (a) having at least one chain-extended polysiloxane cross-linking agent, (b) having at least one hydrophilic vinyl monomer, and (c) a fourth reactive functional group (other than a thiol group) or not A vinyl monomer having a chain transfer agent and / or a fifth reactive functional group (other than an ethylenically unsaturated group), (d) a hydrophobic vinyl monomer, and (e) optionally a polymerizable UV absorber. The polymerizable composition containing is polymerized to form an intermediate copolymer and then reacted with the first or second reactive functional group to form a bond in a coupling reaction in the presence or absence of a coupling agent An ethylenically functionalized intermediate copolymer with an ethylenically functionalized vinyl monomer having a sixth reactive functional group capable of forming a prepolymer. Wherein the fourth, fifth and sixth reactive functional groups are, independently of one another, an amino group -NHR ′ (where R ′ is as defined above), a hydroxyl group The prepolymer according to claim 11, wherein the prepolymer is selected from the group consisting of: a carboxyl group, an acid halide group, an azlactone group, an isocyanate group, an epoxy group, an aziridine group, and combinations thereof. A hydrophilic vinyl-based monomer, a hydrophobic vinyl-based polymer comprising the chain-extended polysiloxane crosslinking agent according to any one of claims 1 to 10 and / or the soluble amphiphilic prepolymer according to claim 11, 12 or 13. Monomers, polysiloxane-containing vinyl monomers, polysiloxane-containing vinyl macromers, crosslinking agents having a molecular weight of less than 700 Daltons, polymerizable UV absorbers, visual colorants, antimicrobial agents, bioactive agents, leachable lubricants A silicone hydrogel material obtained by curing in a mold a lens-forming composition further comprising one or more components selected from the group consisting of leachable tear stabilizers and mixtures thereof, preferably at least An oxygen permeability of about 40 barrer, more preferably at least about 60 barrer, more preferably at least about 80 barrer, .1 MPa to about 2.0 MPa, preferably about 0.2 MPa to about 1.5 MPa, more preferably about 0.3 MPa to about 1.2 MPa, more preferably about 0.4 MPa to about 1.0 MPa, preferably Is at least about 1.0 × 10 ⁻⁵ mm ² / min, more preferably at least about 2.0 × 10 ⁻⁵ mm ² / min, and even more preferably at least about 6.0 × 10 ⁻⁵ mm ² / min. Flux diffusion coefficient D, preferably selected from the group consisting of about 15% to about 55% by weight, more preferably about 20% to about 38% by weight, and combinations thereof when fully hydrated An ophthalmic lens having at least one property.